Influenza and Other Respiratory Viruses: Prevention, Diagnosis, Treatment

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

Deadline for manuscript submissions: 31 August 2024 | Viewed by 9874

Special Issue Editor

Department of Basic and Clinical Sciences, Albany College of Pharmacy and Health Sciences, 106 New Scotland Avenue, Albany, NY 12208, USA
Interests: RNA viruses; influenza; vaccine development; antiviral development; viral immunology; viral pathogenesis; molecular virology; virus–host interaction
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Viral respiratory infections are the most common diseases in humans, contributing to substantial morbidity, mortality, and economic losses annually worldwide. As the world continues to deal with COVID-19, upsurges in infections caused by other respiratory viruses, such as influenza, respiratory syncytial virus, parainfluenza, metapneumovirus, bocaviruses, and non-rhinovirus enteroviruses, have burdened healthcare systems in several countries. Because of their transmissibility, advances in the diagnosis and surveillance of these respiratory viruses are critically needed to guide the use of available therapeutics, the allocation of hospital as well as community resources, and the targeting of vaccination in addition to behavioral change campaigns by public health officials to mitigate their spread. Furthermore, since many of these respiratory viruses have limited therapeutic options and lack effective vaccines, there is an urgent need for further research into the biology of these viruses to help guide the development of effective strategies for the treatment and prevention of infection.

This Special Issue of Viruses seeks to attract original research and review articles focused on (1) advances and innovations in the development of highly sensitive diagnostic tests for the early detection of human respiratory virus infections; (2) timely findings on the epidemiology and transmission of human respiratory viruses; (3) the development and clinical trials of new vaccines, antivirals, and immunotherapeutics for influenza, RSV, coronaviruses, and other clinically relevant human respiratory viruses; (4) studies detailing the effectiveness and/or immunogenicity of existing vaccines; and (5) mitigation measures or strategies to reduce viral transmission/community spread, disease incidence in at-risk populations, and cross-species transmission.

Dr. Eric Yager
Guest Editor

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Keywords

  • influenza
  • adenovirus
  • coronoavirus
  • respiratory syncytial virus
  • rhinovirus
  • respiratory virus
  • antiviral strategies
  • epidemiology
  • diagnosis
  • treatment
  • vaccination
  • surveillance
  • vaccine development

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Published Papers (9 papers)

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Research

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13 pages, 1831 KiB  
Article
Serum Levels of Arachidonic Acid, Interleukin-6, and C-Reactive Protein as Potential Indicators of Pulmonary Viral Infections: Comparative Analysis of Influenza A, Respiratory Syncytial Virus Infection, and COVID-19
by Simona Iftimie, Xavier Gabaldó-Barrios, Joan Penadés-Nadal, Marta Canela-Capdevila, Rubén Piñana, Andrea Jiménez-Franco, Ana F. López-Azcona, Helena Castañé, María Cárcel, Jordi Camps, Antoni Castro and Jorge Joven
Viruses 2024, 16(7), 1065; https://doi.org/10.3390/v16071065 - 1 Jul 2024
Viewed by 869
Abstract
Acute respiratory tract infections, including influenza A (FluA), respiratory syncytial virus (RSV) infection, and COVID-19, can aggravate to levels requiring hospitalization, increasing morbidity and mortality. Identifying biomarkers for an accurate diagnosis and prognosis of these infections is a clinical need. We performed a [...] Read more.
Acute respiratory tract infections, including influenza A (FluA), respiratory syncytial virus (RSV) infection, and COVID-19, can aggravate to levels requiring hospitalization, increasing morbidity and mortality. Identifying biomarkers for an accurate diagnosis and prognosis of these infections is a clinical need. We performed a cross-sectional study aimed to investigate the changes in circulating levels of arachidonic acid, interleukin 6 (IL-6), and C-reactive protein (CRP) in patients with FluA, RSV, or COVID-19, and to analyze the potential of these parameters as diagnosis or prognosis biomarkers. We analyzed serum samples from 172 FluA, 80 RSV, and 217 COVID-19 patients, and 104 healthy volunteers. Individuals with lung viral diseases showed reduced arachidonic acid concentrations compared to healthy people, with these differences being most pronounced in the order COVID-19 > RSV > FluA. Conversely, IL-6 and CRP levels were elevated across diseases, with IL-6 emerging as the most promising diagnostic biomarker, with areas under the curve (AUC) of the receiver operating characteristics plot higher than 0.85 and surpassing arachidonic acid and CRP. Moreover, IL-6 displayed notable efficacy in distinguishing between FluA patients who survived and those who did not (AUC = 0.80). These findings may provide useful tools for diagnosing and monitoring the severity of acute viral respiratory tract infections, ultimately improving patient outcomes. Full article
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20 pages, 3557 KiB  
Article
Whole-Genome Sequencing and Genetic Diversity of Human Respiratory Syncytial Virus in Patients with Influenza-like Illness in Sicily (Italy) from 2017 to 2023
by Fabio Tramuto, Carmelo Massimo Maida, Giulia Randazzo, Valeria Guzzetta, Arianna Santino, Rita Li Muli, Claudio Costantino, Giorgio Graziano, Emanuele Amodio, Walter Mazzucco and Francesco Vitale
Viruses 2024, 16(6), 851; https://doi.org/10.3390/v16060851 - 26 May 2024
Viewed by 1030
Abstract
Monitoring the genetic variability of human respiratory syncytial virus (hRSV) is of paramount importance, especially for the potential implication of key antigenic mutations on the emergence of immune escape variants. Thus, to describe the genetic diversity and evolutionary dynamics of hRSV circulating in [...] Read more.
Monitoring the genetic variability of human respiratory syncytial virus (hRSV) is of paramount importance, especially for the potential implication of key antigenic mutations on the emergence of immune escape variants. Thus, to describe the genetic diversity and evolutionary dynamics of hRSV circulating in Sicily (Italy), a total of 153 hRSV whole-genome sequences collected from 770 hRSV-positive subjects between 2017 and 2023, before the introduction of expanded immunization programs into the population, were investigated. The phylogenetic analyses indicated that the genotypes GA.2.3.5 (ON1) for hRSV-A and GB.5.0.5a (BA9) for hRSV-B co-circulated in our region. Amino acid (AA) substitutions in the surface and internal proteins were evaluated, including the F protein antigenic sites, as the major targets of immunoprophylactic monoclonal antibodies and vaccines. Overall, the proportion of AA changes ranged between 1.5% and 22.6% among hRSV-A, whereas hRSV-B varied in the range 0.8–16.9%; the latter was more polymorphic than hRSV-A within the key antigenic sites. No AA substitutions were found at site III of both subgroups. Although several non-synonymous mutations were found, none of the polymorphisms known to potentially affect the efficacy of current preventive measures were documented. These findings provide new insights into the global hRSV molecular epidemiology and highlight the importance of defining a baseline genomic picture to monitor for future changes that might be induced by the selective pressures of immunological preventive measures, which will soon become widely available. Full article
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9 pages, 504 KiB  
Communication
Impact of the H274Y Substitution on N1, N4, N5, and N8 Neuraminidase Enzymatic Properties and Expression in Reverse Genetic Influenza A Viruses
by Alexandre Gaymard, Caroline Picard, Guilhem Vazzoler, Pascale Massin, Emilie Frobert, Murielle Sabatier, Mendy Barthelemy, Martine Valette, Michèle Ottmann, Jean-Sébastien Casalegno, Bruno Lina and Vanessa Escuret
Viruses 2024, 16(3), 388; https://doi.org/10.3390/v16030388 - 1 Mar 2024
Viewed by 1073
Abstract
The H274Y substitution (N2 numbering) in neuraminidase (NA) N1 confers oseltamivir resistance to A(H1N1) influenza viruses. This resistance has been associated with reduced N1 expression using transfected cells, but the effect of this substitution on the enzymatic properties and on the expression of [...] Read more.
The H274Y substitution (N2 numbering) in neuraminidase (NA) N1 confers oseltamivir resistance to A(H1N1) influenza viruses. This resistance has been associated with reduced N1 expression using transfected cells, but the effect of this substitution on the enzymatic properties and on the expression of other group-1-NA subtypes is unknown. The aim of the present study was to evaluate the antiviral resistance, enzymatic properties, and expression of wild-type (WT) and H274Y-substituted NA for each group-1-NA. To this end, viruses with WT or H274Y-substituted NA (N1pdm09 or avian N4, N5 or N8) were generated by reverse genetics, and for each reverse-genetic virus, antiviral susceptibility, NA affinity (Km), and maximum velocity (Vm) were measured. The enzymatic properties were coupled with NA quantification on concentrated reverse genetic viruses using mass spectrometry. The H274Y-NA substitution resulted in highly reduced inhibition by oseltamivir and normal inhibition by zanamivir and laninamivir. This resistance was associated with a reduced affinity for MUNANA substrate and a conserved Vm in all viruses. NA quantification was not significantly different between viruses carrying WT or H274Y-N1, N4 or N8, but was lower for viruses carrying H274Y-N5 compared to those carrying a WT-N5. In conclusion, the H274Y-NA substitution of different group-1-NAs systematically reduced their affinity for MUNANA substrate without a significant impact on NA Vm. The impact of the H274Y-NA substitution on viral NA expression was different according to the studied NA. Full article
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10 pages, 1738 KiB  
Article
Influenza A, like Omicron SARS-CoV-2, Is Similarly Detected in Saliva or Nasopharyngeal Samples via RT-qPCR
by Hellen Abreu, Carla Adriane Royer, Carolina Gracia Poitevin, Ana Flávia Kohler, Ana Carolina Rodrigues, Sonia Mara Raboni, Meri Bordignon Nogueira, Pedro Henrique Cardoso, Monica Barcellos Arruda, Patrícia Alvarez da Silva Baptista, Ana Claudia Bonatto, Daniela Fiori Gradia, Douglas Adamoski, Emanuel Maltempi de Souza and Jaqueline Carvalho de Oliveira
Viruses 2023, 15(12), 2352; https://doi.org/10.3390/v15122352 - 30 Nov 2023
Viewed by 1049
Abstract
After the Coronavirus pandemic, the importance of virus surveillance was highlighted, reinforcing the constant necessity of discussing and updating the methods for collection and diagnoses, including for other respiratory viruses. Although the nasopharyngeal swab is the gold-standard sample for detecting and genotyping SARS-CoV-2 [...] Read more.
After the Coronavirus pandemic, the importance of virus surveillance was highlighted, reinforcing the constant necessity of discussing and updating the methods for collection and diagnoses, including for other respiratory viruses. Although the nasopharyngeal swab is the gold-standard sample for detecting and genotyping SARS-CoV-2 and Influenza viruses, its collection is uncomfortable and requires specialized teams, which can be costly. During the pandemic, non-invasive saliva samples proved to be a suitable alternative for SARS-CoV-2 diagnosis, but for Influenza virus the use of this sample source is not recognized yet. In addition, most SARS-CoV-2 comparisons were conducted before the Omicron variant emerged. Here, we aimed to compare Influenza A and Omicron RT-qPCR analysis of nasopharyngeal swabs and saliva self-collection in paired samples from 663 individuals. We found that both nasopharyngeal swab and saliva collection are efficient for the diagnosis of Omicron (including sub-lineages) and for Influenza A, with high sensitivity and accuracy (>90%). The kappa index is 0.938 for Influenza A and 0.905 for SARS-CoV-2. These results showed excellent agreement between the two samples reinforcing saliva samples as a reliable source for detecting Omicron and highlighting saliva as a valid sample source for Influenza detection, considering this cheaper and more comfortable alternative. Full article
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Review

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14 pages, 2991 KiB  
Review
Does Prior Respiratory Viral Infection Provide Cross-Protection Against Subsequent Respiratory Viral Infections? A Systematic Review and Meta-Analysis
by Vennila Gopal, Matthew Chung Yi Koh, Jinghao Nicholas Ngiam, Ong Hang-Cheng, Jyoti Somani, Paul Anatharajah Tambyah and Jeremy Tey
Viruses 2024, 16(6), 982; https://doi.org/10.3390/v16060982 - 19 Jun 2024
Viewed by 610
Abstract
The epidemiology of different respiratory viral infections is believed to be affected by prior viral infections in addition to seasonal effects. This PROSPERO-registered systematic review identified 7388 studies, of which six met our criteria to answer the question specifically. The purpose of this [...] Read more.
The epidemiology of different respiratory viral infections is believed to be affected by prior viral infections in addition to seasonal effects. This PROSPERO-registered systematic review identified 7388 studies, of which six met our criteria to answer the question specifically. The purpose of this review was to compare the prevalence of sequential viral infections in those with previously documented positive versus negative swabs. The pooled prevalence of sequential viral infections over varying periods from 30–1000 days of follow-up was higher following a negative respiratory viral swab at 0.15 than following a positive swab at 0.08, indicating the potential protective effects of prior respiratory viral infections. However, significant heterogeneity and publication biases were noted. There is some evidence, albeit of low quality, of a possible protective effect of an initial viral infection against subsequent infections by a different virus, which is possibly due to broad, nonspecific innate immunity. Future prospective studies are needed to validate our findings. Full article
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Other

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10 pages, 771 KiB  
Brief Report
Prevalence of Co-Infections in Primary Care Patients with Medically Attended Acute Respiratory Infection in the 2022/2023 Season
by Maja Sočan, Katarina Prosenc and Maja Mrzel
Viruses 2024, 16(8), 1289; https://doi.org/10.3390/v16081289 - 13 Aug 2024
Viewed by 213
Abstract
In the post-pandemic period, an endemic circulation of respiratory viruses has been re-established. Respiratory viruses are co-circulating with SARS-CoV-2. We performed a retrospective analysis of co-infections in primary care patients with medically attended acute respiratory infections (MAARI) who consulted from week 40/2022 to [...] Read more.
In the post-pandemic period, an endemic circulation of respiratory viruses has been re-established. Respiratory viruses are co-circulating with SARS-CoV-2. We performed a retrospective analysis of co-infections in primary care patients with medically attended acute respiratory infections (MAARI) who consulted from week 40/2022 to week 39/2023 and were tested for a panel of respiratory viruses. Out of 2099 samples tested, 1260 (60.0%) were positive for one virus. In 340 samples, co-infection was detected: two viruses in 281 (13.4%), three viruses in 51 (2.4%), and four viruses in eight (0.4%) samples. Respiratory viruses co-infected the patients with MAARI at very different rates. The lowest rates of co-infections were confirmed for influenza B (13.8%) and influenza A (22.9%) and the highest for human bocaviruses (84.0%) and human parechoviruses (82.1%). Co-infections were detected in 28.2% of SARS-CoV-2 positive samples. SARS-CoV-2 has never been co-infected with influenza B virus, enterovirus or adenovirus, although the latter was found as a co-infecting virus with all other respiratory viruses tested. The rate of co-infections decreased significantly with increasing age (p-value 0.000), and no difference was found regarding gender (p-value 0.672). It is important to understand the epidemiology of respiratory co-infections for prevention and management decisions in patients with MAARI. Full article
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8 pages, 1755 KiB  
Brief Report
Influenza Virus Genomic Surveillance, Arizona, USA, 2023–2024
by Rabia Maqsood, Matthew F. Smith, LaRinda A. Holland, Regan A. Sullins, Steven C. Holland, Michelle Tan, Gabrielle M. Hernandez Barrera, Alexis W. Thomas, Mario Islas, Joanna L. Kramer, Lora Nordstrom, Mary Mulrow, Michael White, Vel Murugan and Efrem S. Lim
Viruses 2024, 16(5), 692; https://doi.org/10.3390/v16050692 - 27 Apr 2024
Cited by 1 | Viewed by 1121
Abstract
Influenza viruses are constantly evolving and are therefore monitored worldwide in the hope to reduce the burden of disease by annual updates to vaccine recommendations. We conducted genomic sequencing of 110 influenza A and 30 influenza B viruses from specimens collected between October [...] Read more.
Influenza viruses are constantly evolving and are therefore monitored worldwide in the hope to reduce the burden of disease by annual updates to vaccine recommendations. We conducted genomic sequencing of 110 influenza A and 30 influenza B viruses from specimens collected between October 2023 and February 2024 in Arizona, USA. We identified mutations in the hemagglutinin (HA) antigenic sites as well as the neuraminidase (NA) gene in our samples. We also found no unique HA and NA mutations in vaccinated yet influenza-infected individuals. Real-time genomic sequencing surveillance is important to ensure influenza vaccine effectiveness. Full article
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10 pages, 598 KiB  
Case Report
Sudden Infant Death Associated with Rhinovirus Infection
by Christelle Auvray, Stéphanie Perez-Martin, Isabelle Schuffenecker, Cécile Pitoiset, Georges Tarris, Katia Ambert-Balay, Laurent Martin, Nathalie Dullier-Taillefumier, Jean-Baptiste Bour and Catherine Manoha
Viruses 2024, 16(4), 518; https://doi.org/10.3390/v16040518 - 27 Mar 2024
Viewed by 1214
Abstract
A less than one-month-old infant with symptoms of rhinitis died unexpectedly in his sleep. He was not born prematurely and had no known underlying disease. Cerebrospinal fluid, nasopharyngeal and lung samples, and rectal swab were found to be positive for subgroup A rhinovirus, [...] Read more.
A less than one-month-old infant with symptoms of rhinitis died unexpectedly in his sleep. He was not born prematurely and had no known underlying disease. Cerebrospinal fluid, nasopharyngeal and lung samples, and rectal swab were found to be positive for subgroup A rhinovirus, while the blood was negative. This case highlights the important finding that the rhinovirus, a common pathogen associated with upper respiratory tract infections, can sometimes, as the only pathogen, lead to complications such as a cerebrospinal infection and be involved in the sudden infant death syndrome (SIDS). Vigilance is necessary in case of viral infections in the infant’s environment, and measures of hygiene and protection must be encouraged in order to reduce the risk of the SIDS. Full article
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9 pages, 1132 KiB  
Brief Report
Temporal Shift of the Respiratory Syncytial Virus Epidemic Peak for the Years 2020–2023 in Marseille, Southern France
by Lucille Claire De Maria, Philippe Colson, Aurélie Morand, Noémie Vanel, Didier Stoupan, Bernard La Scola and Céline Boschi
Viruses 2023, 15(8), 1671; https://doi.org/10.3390/v15081671 - 31 Jul 2023
Cited by 1 | Viewed by 1544
Abstract
Respiratory syncytial virus is among the most common causes of respiratory infections. Typically, this viral infection has a seasonality during the cold months but with the SARS-CoV-2 pandemic this has been considerably modified. Here, we studied the epidemiology of this virus in university [...] Read more.
Respiratory syncytial virus is among the most common causes of respiratory infections. Typically, this viral infection has a seasonality during the cold months but with the SARS-CoV-2 pandemic this has been considerably modified. Here, we studied the epidemiology of this virus in university hospitals of Marseille, South of France, over the period 2020 to 2023. We tested in our laboratory from July 2020 to October 2021 16,516 nasopharyngeal swabs from 16,468 patients for RSV infection using different qPCR assays. We then analyzed data from previous and subsequent winters (from 2018 to 2023) and previous summers (from 2015 to 2021). A total of 676 patients were RSV-positive; their mean age was 3 years and 91 were under 5 years of age. We observed a delay of 4 months of the RSV epidemic’s onset compared to other years with an epidemic that peaked in March 2021. We had significantly more RSV-positive cases during summer 2021 compared to previous summers, whereas the incidence of RSV infections was not significantly higher during winter 2022 versus previous winters. Moreover, 494 patients were diagnosed as RSV-positive in the emergency unit and 181 were subsequently hospitalized, and 34 patients were diagnosed RSV-positive while already in the intensive care unit. Over all the study periods, 38 patients diagnosed as RSV-positive died, the majority of whom (23/28) were over 65 years of age. These data show an atypical evolution of the incidence of RSV infections in our city and is another example of the unpredictability of infectious disease epidemiology. Full article
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