The rinovirus is a highly prevalent viral pathogen belonging to the Picornaviridae family and is the leading cause of the common cold, accounting for approximately 35–50% of all cases in adults and children [1]. With over 160 identified serotypes classified into three species—rhinovirus A, rhinovirus B, and rhinovirus C—its extensive genetic diversity enables frequent reinfections and complicates vaccine development [2]. The virus primarily infects the upper respiratory tract, replicating optimally at the cooler temperatures (33–35 °C) found in the nasal passages, which explains its tropism for the nose and associated symptoms such as nasal congestion, rhinorrhea, sneezing, sore throat, and cough [3]. Transmission occurs via respiratory droplets, aerosols, and contact with contaminated surfaces, making it highly contagious in crowded environments like schools and offices [4]. While most infections are mild and self-limiting, lasting 7–10 days, rinovirus can trigger severe complications such as bronchitis, bronchiolitis, sinusitis, and otitis media, particularly in vulnerable populations including infants, the elderly, and individuals with preexisting conditions like asthma or chronic obstructive pulmonary disease (COPD) [5]. In immunocompromised patients, it may lead to lower respiratory tract infections, including pneumonia [6]. Diagnosis is typically clinical, but molecular methods such as polymerase chain reaction (PCR) are used in high-risk cases to confirm infection and guide management [7]. No specific antiviral treatments or vaccines are currently available, so management focuses on symptomatic relief through rest, hydration, and over-the-counter medications, while prevention relies on hygiene measures like handwashing and surface disinfection [2]. Surveillance systems such as RespiVirNet monitor viral circulation, revealing that rinovirus remains a dominant respiratory pathogen, often surpassing SARS-CoV-2 and other respiratory viruses in prevalence during certain seasons [9].

Virology and Molecular Biology

The rinovirus is a member of the Picornaviridae family and exhibits distinct virological and molecular characteristics that define its pathogenicity, tropism, and persistence in human populations. As a non-enveloped virus with a single-stranded, positive-sense RNA genome, it possesses structural and replicative features that distinguish it from other respiratory pathogens and contribute to its high prevalence and ability to cause recurrent infections [1].

Structure and Genome Organization

Rinoviruses are non-enveloped viruses, meaning they lack a lipid bilayer envelope, which enhances their environmental stability but renders them more susceptible to desiccation and certain disinfectants compared to enveloped viruses like SARS-CoV-2 or influenza virus [11]. The virion is approximately 30 nm in diameter and features an icosahedral capsid composed of 60 protomers, each made up of four viral proteins: VP1, VP2, VP3, and VP4 [12]. The capsid encloses a single-stranded RNA genome of positive polarity, approximately 7.2–7.5 kb in length, which functions directly as messenger RNA (mRNA) upon entry into the host cell [1].

The genome contains a single open reading frame that is translated into a large polyprotein, subsequently cleaved by viral proteases into structural and non-structural proteins essential for replication. A key feature of the genome is the presence of an internal ribosome entry site (IRES) in the 5' untranslated region (5' UTR), which allows cap-independent translation initiation, enabling efficient protein synthesis even under cellular stress conditions [14]. This IRES is highly conserved and is frequently targeted in diagnostic assays such as polymerase chain reaction (PCR) for virus detection [15].

Receptor Usage and Cellular Entry

Rinoviruses enter host cells through receptor-mediated endocytosis, with different serotypes utilizing distinct cellular receptors. Approximately 90% of rhinovirus A and B serotypes bind to intercellular adhesion molecule-1 (ICAM-1), a surface protein expressed on respiratory epithelial cells [16]. The interaction between the viral capsid and ICAM-1 triggers conformational changes in the virion, leading to the externalization of the N-terminus of VP1 and the release of VP4. This facilitates the formation of a pore in the endosomal membrane, allowing the viral RNA to be released into the cytoplasm [17].

A smaller subset of rhinoviruses, particularly certain rhinovirus B types, use the low-density lipoprotein receptor (LDLR) for cellular entry [18]. In contrast, rhinovirus C, which is associated with more severe respiratory disease, utilizes cadherin-related family member 3 (CDHR3) as its receptor, a protein with genetic variants linked to increased susceptibility to asthma [19].

Replication Cycle

Following endocytosis and uncoating in the acidic environment of the endosome, the positive-sense RNA genome is released into the host cytoplasm. It is immediately translated by host ribosomes into the viral polyprotein, which is then processed by viral proteases, including 3C protease (3Cpro), a key enzyme in the maturation of viral proteins [20]. The 3Cpro is a major target for antiviral drug development due to its essential role and high degree of conservation across serotypes [21].

Viral RNA replication occurs in association with host cell membranes, where the viral RNA-dependent RNA polymerase (3Dpol) synthesizes a complementary negative-strand RNA, which then serves as a template for the production of new positive-sense genomic RNA [22]. These new genomes are packaged into newly assembled capsids, and mature virions are released from the cell, often through lysis, to infect neighboring cells.

Temperature Sensitivity and Tissue Tropism

A defining biological feature of rinoviruses is their thermolability: they replicate optimally at temperatures of 33–35 °C, which correspond to the temperature of the nasal passages [3]. This explains their tropism for the upper respiratory tract and the predominance of symptoms such as nasal congestion and rhinorrhea. In contrast, they replicate poorly at core body temperature (37 °C), limiting their ability to infect the lower respiratory tract in most individuals [12].

This temperature dependence also influences the host immune response, as interferon production by nasal epithelial cells is less robust at cooler temperatures, facilitating viral evasion of the innate immune system [25].

Genetic Diversity and Antigenic Variation

Rinoviruses exhibit extraordinary genetic diversity, with over 160 identified serotypes classified into three species: rhinovirus A, rhinovirus B, and rhinovirus C [26]. This diversity arises from high mutation rates during RNA replication—due to the error-prone nature of the viral RNA polymerase—and recombination events between strains [27]. The extensive antigenic variation among serotypes prevents long-lasting immunity and allows for frequent reinfections, posing a major challenge for the development of a universal vaccine [28].

The discovery of rhinovirus C in 2006, enabled by advanced sequencing techniques, underscored the limitations of traditional culture-based detection methods and highlighted the ongoing evolution of diagnostic and surveillance strategies [29]. This genetic heterogeneity also complicates antiviral development, as drugs or antibodies effective against one serotype may not be effective against others [30].

Immune Evasion Mechanisms

Rinoviruses employ multiple strategies to evade the host’s innate immune response. A critical mechanism is the inhibition of type I interferon (IFN-α/β) production, which is essential for antiviral defense. The virus interferes with the activation of transcription factors such as IRF-3, thereby suppressing interferon signaling [31]. Additionally, the viral 3C protease cleaves key signaling molecules like TRIF, MAVS, and IRF-7, disrupting downstream antiviral pathways [20].

The virus also modulates the host inflammatory response by inducing the expression of immunosuppressive cytokines such as IL-10 and immune checkpoint molecules like PD-L1, which inhibit T-cell activity and promote viral persistence [33]. These immune evasion tactics are particularly effective in individuals with preexisting respiratory conditions like asthma or chronic obstructive pulmonary disease (COPD), where baseline immune responses are already dysregulated [34].

Classification and Serotypes

The rinovirus is classified within the family Picornaviridae and the genus Enterovirus, a reclassification supported by phylogenetic analyses that revealed its close genetic relationship with human enteroviruses [28]. Historically considered a distinct genus, the International Committee on Taxonomy of Viruses (ICTV) now officially groups rinoviruses under Enterovirus, reflecting their shared genomic and structural features with other members of this genus [28]. This classification underscores the evolutionary and biological continuity between rinoviruses and enteroviruses, despite their differing clinical presentations.

Species and Genotypic Diversity

Rinoviruses are divided into three primary species: Rhinovirus A (RV-A), Rhinovirus B (RV-B), and Rhinovirus C (RV-C). This classification is based on genetic sequencing, particularly of the capsid proteins (VP1, VP2, VP3) and the highly conserved 5' untranslated region (5' UTR), which is frequently targeted in molecular diagnostic assays [15]. The identification of over 170 distinct genotypes highlights the virus's extraordinary genetic diversity, with approximately 83 types in RV-A, 32 in RV-B, and 56 in RV-C [38].

The discovery of RV-C in 2006 was a significant advancement, made possible by non-targeted genome sequencing techniques that could detect the virus without prior amplification [29]. This late identification explains why RV-C was not recognized alongside the earlier RV-A and RV-B species. The vast number of serotypes is a key factor in the virus's ability to cause frequent reinfections, as immunity to one serotype does not confer protection against others, posing a major obstacle to vaccine development [2].

Clinical Significance of Species

The three species exhibit notable differences in pathogenicity and clinical impact, which have important implications for disease prognosis and management.

Rhinovirus A (RV-A)

RV-A is associated with more severe infections compared to RV-B and is frequently implicated in lower respiratory tract infections. It is a common trigger for exacerbations of chronic respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD) [1]. Certain RV-A serotypes are known to cause more intense symptoms, including wheezing and prolonged illness duration, making this species a significant concern in vulnerable populations [42].

Rhinovirus B (RV-B)

RV-B generally causes milder, and often asymptomatic, infections. It is less frequently linked to severe respiratory complications compared to RV-A and RV-C [1]. While some RV-B serotypes can contribute to exacerbations in predisposed individuals, its overall clinical impact is considered less severe.

Rhinovirus C (RV-C)

RV-C has emerged as the most pathogenic of the three species. It is strongly associated with severe respiratory infections, particularly in children, and is a leading cause of bronchiolitis, pneumonia, and hospitalizations [44]. RV-C is a key player in acute exacerbations of asthma and COPD, contributing significantly to airway inflammation and a decline in pulmonary function [45]. Its high transmissibility and ability to replicate efficiently in the lower airways make it a pathogen of major clinical relevance, especially in pediatric and immunocompromised patients [46].

Diagnostic and Surveillance Implications

The genetic classification of rinoviruses has direct consequences for diagnosis and public health surveillance. Molecular methods, particularly polymerase chain reaction (PCR), are essential for detecting the virus. Real-time RT-PCR targeting the conserved 5' UTR region is highly sensitive and specific, making it the gold standard for laboratory diagnosis [47]. However, the high genetic similarity between rinoviruses and enteroviruses can lead to cross-reactivity in some assays, necessitating gene sequencing for precise species-level identification [48].

In Italy, the RespiVirNet surveillance system, managed by the Istituto Superiore di Sanità (ISS), monitors the seasonal circulation and genetic diversity of respiratory viruses, including the different genotypes of RV-A, RV-B, and RV-C [49]. This integrated virological surveillance is crucial for tracking the emergence of new variants, understanding seasonal trends, and informing public health responses to respiratory virus activity.

Transmission and Epidemiology

The rinovirus is a highly contagious pathogen that spreads efficiently within human populations, particularly in crowded or enclosed environments. Its transmission occurs through multiple routes, contributing to its status as the most prevalent cause of the common cold and a significant driver of respiratory illness globally [4]. The virus’s ability to persist on surfaces, combined with its high serotype diversity and seasonal patterns, underpins its widespread epidemiological impact.

Modes of Transmission

Rinovirus transmission primarily occurs through three interconnected pathways: respiratory droplets, aerosols, and fomite-mediated contact. When an infected individual coughs, sneezes, or speaks, they release virus-laden droplets into the air, which can be inhaled by nearby individuals or settle on surfaces [18]. These droplets, typically larger than 5–10 microns, are a major source of direct transmission. Additionally, smaller particles (<5 microns) can remain suspended in the air as aerosols, especially in poorly ventilated indoor spaces, enabling longer-range dissemination [52].

A critical factor in rinovirus spread is its environmental stability. The virus can survive for several hours to days on inanimate surfaces such as doorknobs, telephones, toys, and countertops, particularly on non-porous materials like plastic and metal [53]. Transmission via fomites occurs when individuals touch contaminated surfaces and subsequently transfer the virus to their mucous membranes—nose, mouth, or eyes—through hand contact. This route is especially significant in high-touch environments like schools, daycare centers, and healthcare facilities [54].

Direct person-to-person contact, such as handshakes, also facilitates transmission, particularly when hygiene practices are inadequate. The high transmissibility of the virus is further amplified by the fact that individuals are most contagious during the first 2–3 days of symptom onset, coinciding with peak viral shedding [55]. However, asymptomatic or presymptomatic shedding may also contribute to silent spread, particularly in children, who often serve as reservoirs in community settings [56].

Seasonal Patterns and Environmental Influences

Rinovirus exhibits a distinct seasonal epidemiology, with increased circulation during the autumn and spring months in temperate climates. Unlike influenza, which peaks sharply in winter, rinovirus maintains a more sustained presence throughout the year, often dominating respiratory virus detections during transitional seasons [57]. In Italy, surveillance data from the RespiVirNet system indicate significant activity in October and November, followed by a secondary peak in March [58]. Notably, rinovirus remains the most frequently isolated respiratory virus even during summer months, underscoring its year-round relevance [57].

Environmental conditions play a crucial role in viral transmission. Low relative humidity (≤23%) enhances the stability and infectivity of airborne rinovirus, with survival rates reaching 71–77%, whereas higher humidity (>43%) reduces infectivity to below 22% [60]. Maintaining indoor humidity around 40% is therefore recommended to limit viral persistence. Additionally, cooler temperatures (33–35 °C), typical of the nasal passages, favor viral replication and may contribute to increased transmission during colder months [54]. The tendency for people to congregate indoors during these periods further amplifies the risk of transmission through close contact and poor ventilation [62].

Population Susceptibility and Risk Factors

Certain populations are at heightened risk for severe rinovirus infections. Young children, especially those under five years of age, are disproportionately affected, with high rates of infection due to immature immune systems and frequent exposure in daycare and school settings [63]. Data from RespiVirNet show that children under five experience approximately 50 cases per 1,000 individuals during peak weeks, making them the most impacted demographic [63].

Other vulnerable groups include the elderly (over 65 years), whose age-related decline in immune function increases susceptibility to complications, and individuals with chronic respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD). In these patients, rinovirus infection is a leading trigger of acute exacerbations, contributing to hospitalizations and increased morbidity [65]. Immunocompromised individuals, including those with primary immunodeficiencies or on immunosuppressive therapy, are also at risk for prolonged or severe lower respiratory tract infections, including pneumonia [66].

Key predisposing factors include prematurity, exposure to secondhand smoke, underlying comorbidities (e.g., cardiovascular disease, diabetes), and suboptimal control of chronic conditions. Environmental factors such as overcrowding and poor indoor air quality further elevate transmission risk [67].

Epidemiological Surveillance and Modeling

Effective monitoring of rinovirus circulation relies on integrated surveillance systems such as RespiVirNet in Italy, coordinated by the Istituto Superiore di Sanità (ISS) [49]. This system combines clinical reporting from general practitioners and pediatricians with virological testing from regional laboratories to track the incidence of acute respiratory infections (ARI) and identify circulating pathogens. Weekly reports, such as RespiNews, provide real-time data on viral prevalence, showing that rinovirus often accounts for nearly half of all detected respiratory viruses during peak seasons [69].

Globally, surveillance is less centralized, but programs like the U.S. Centers for Disease Control and Prevention (CDC)’s National Respiratory and Enteric Virus Surveillance System (NREVSS) and the Department of Defense Global Respiratory Pathogen Surveillance Program (DoD GRPSP) include rinovirus monitoring [70]. Environmental surveillance, including wastewater analysis, has emerged as a valuable tool for detecting viral circulation independent of clinical reporting, offering insights into community-level transmission dynamics [71].

Mathematical modeling, such as the SIR (Susceptible–Infected–Recovered) and SEIR (Susceptible–Exposed–Infected–Recovered) models, is used to simulate rinovirus transmission and predict epidemic trends [72]. These models incorporate data on contact rates, viral shedding, and population immunity to estimate the basic reproduction number (R0) and evaluate the impact of interventions. However, the high serotype diversity and lack of durable immunity complicate long-term forecasting, necessitating continuous data integration from surveillance networks.

Public Health Implications

The high transmissibility and year-round circulation of rinovirus impose a substantial burden on public health systems, particularly during seasonal peaks. In the 2024–2025 season, RespiVirNet reported over 500,000 new ARI cases in a single week, with rinovirus as a dominant pathogen [73]. The virus not only causes widespread mild illness but also contributes to absenteeism in schools and workplaces, and drives healthcare utilization through exacerbations of chronic conditions.

Prevention strategies focus on hygiene measures, including frequent handwashing with soap and water or use of alcohol-based sanitizers, avoiding close contact with symptomatic individuals, and disinfecting frequently touched surfaces [2]. Respiratory etiquette, such as covering coughs and sneezes with the elbow or a tissue, is also emphasized. Although no vaccine exists due to the vast number of serotypes, promoting general respiratory hygiene and vaccination against other pathogens like influenza and SARS-CoV-2 can reduce the risk of coinfections and alleviate strain on healthcare systems [2].

In conclusion, the transmission and epidemiology of rinovirus are shaped by its efficient spread through multiple routes, seasonal patterns influenced by environmental conditions, and disproportionate impact on vulnerable populations. Robust surveillance, public health education, and targeted prevention efforts remain essential to mitigate its widespread health and societal effects.

Clinical Manifestations and Complications

The clinical manifestations of rinovirus infection are primarily confined to the upper respiratory tract, resulting in the classic symptoms of the common cold. However, in vulnerable populations, the virus can lead to significant complications involving the lower respiratory tract and exacerbate preexisting chronic conditions. The typical illness is mild and self-limiting, with symptoms appearing 12 to 72 hours after exposure and lasting an average of 7 to 10 days, although they can persist for up to 14 days in some individuals [2]. The severity of symptoms is influenced by the host's immune response, particularly the speed and efficacy of the nasal cellular response to the viral infection [77].

Typical Symptoms of the Common Cold

The hallmark symptoms of a rinovirus infection are a direct result of the virus's tropism for the nasal passages and upper airways, where it replicates optimally at the cooler temperatures of 33–35 °C [3]. The most common symptoms include:

  • Nasal congestion and rhinorrhea (runny nose): Often the first signs of infection, nasal secretions typically start clear and watery before becoming thicker and more opaque [2].
  • Sneezing: A frequent symptom, particularly in the early stages of infection, as a reflex to nasal irritation [2].
  • Sore throat: Present in approximately 60% of cases, caused by inflammation of the pharynx [81].
  • Cough: Usually dry and non-productive, it can persist for 10 to 15 days even after other symptoms have resolved [82].
  • General malaise and headache: Mild systemic symptoms are common, along with muscle aches and a general feeling of being unwell [82].
  • Low-grade fever: More common in children than in adults, where it is often absent or very mild [53].
  • Reduced sense of smell and facial pain: Resulting from inflammation of the nasal passages and sinuses, leading to olfactory dysfunction and pressure in the facial bones [85].

The peak of symptoms typically occurs between 1 and 3 days after exposure, which coincides with the period of highest viral shedding and contagiousness [82].

Complications and Exacerbations of Chronic Diseases

Although most rinovirus infections are benign, the virus can trigger serious complications, especially in individuals with compromised immune systems or preexisting respiratory conditions. These complications extend beyond the upper respiratory tract and can involve the lower airways, leading to significant morbidity.

Lower Respiratory Tract Infections

In susceptible populations, the infection can progress to the lower respiratory tract, causing:

  • Bronchitis: An inflammation of the bronchial tubes, often characterized by a persistent cough and mucus production [87].
  • Bronchiolitis: A more severe condition involving inflammation of the bronchioles, particularly in infants and young children. It can lead to significant respiratory distress and is a common reason for hospitalization in this age group [88].
  • Pneumonia: In rare cases, particularly in immunocompromised patients or those with underlying lung disease, rinovirus can cause viral pneumonia [6].

Secondary Bacterial Infections

The inflammation and obstruction caused by the viral infection can create an environment conducive to secondary bacterial infections. Common complications include:

  • Sinusitis: Inflammation of the sinuses due to blocked drainage pathways and mucus buildup [5].
  • Otitis media: A middle ear infection, especially prevalent in young children, where the Eustachian tube becomes blocked, allowing bacteria to proliferate [5].

Exacerbations of Chronic Respiratory Diseases

Rinovirus is a major trigger for acute exacerbations of chronic respiratory diseases, significantly impacting patient health and healthcare utilization.

  • Asthma: The virus is the most common viral trigger of asthma exacerbations, particularly in children. Infections can provoke bronchoconstriction, wheezing, and increased mucus production, leading to acute asthma attacks [2]. The risk is even higher when a viral infection coincides with allergen exposure, creating a synergistic effect that amplifies airway inflammation [93]. There is also evidence that early-life infections with rhinovirus C (RV-C) are associated with an increased risk of developing persistent asthma [94].
  • Chronic obstructive pulmonary disease (COPD): In patients with COPD, rinovirus infections are a leading cause of acute exacerbations. These events are characterized by a worsening of dyspnea, cough, and sputum production, and are linked to accelerated lung function decline, increased hospitalization rates, and higher mortality [65]. The virus is one of the most frequently identified pathogens during COPD exacerbations, alongside influenza and the respiratory syncytial virus (RSV) [96].

The heightened risk in these populations is due to a combination of factors, including an impaired innate immune response, such as a reduced production of interferons (IFN-β and IFN-λ), which allows for greater viral replication, and a preexisting state of airway inflammation that is easily amplified by the viral infection [33].

Populations at High Risk for Severe Complications

Certain groups are particularly vulnerable to severe complications from rinovirus infection:

  • Infants and young children: Their immature immune systems and smaller airways make them more susceptible to lower respiratory tract infections like bronchiolitis and pneumonia [98].
  • The elderly (over 65 years): Age-related decline in immune function (immunosenescence) and a higher prevalence of comorbidities increase the risk of severe disease and hospitalization [99].
  • Immunocompromised individuals: Patients with primary or secondary immunodeficiencies, such as those undergoing immunosuppressive therapy or living with HIV, are at risk for prolonged, severe, or disseminated infections [66].
  • Patients with chronic conditions: Those with preexisting respiratory diseases like asthma and chronic obstructive pulmonary disease (COPD), as well as other comorbidities such as heart disease or diabetes, are at a significantly higher risk of complications [101].

Favorable conditions for transmission, such as crowded environments (e.g., schools, daycare centers, nursing homes), and exposure to environmental factors like secondhand smoke, further increase the risk for these vulnerable populations [67].

Diagnosis and Laboratory Testing

The diagnosis of rinovirus infection is primarily clinical, based on the characteristic symptoms of the common cold such as nasal congestion, rhinorrhea, sneezing, sore throat, and mild cough, typically without high fever [2]. However, in high-risk populations or complex clinical scenarios, laboratory confirmation becomes essential to guide management and prevent complications. The most sensitive and specific method for detecting rinovirus is molecular testing, particularly reverse transcription polymerase chain reaction (RT-PCR), which allows for the amplification and identification of viral RNA from clinical samples [7].

Molecular Methods: RT-PCR as the Gold Standard

The RT-PCR in real time (real-time RT-PCR) is considered the gold standard for laboratory diagnosis of rinovirus due to its high sensitivity and specificity, often exceeding 95% [7]. This technique detects the viral RNA in specimens collected via nasopharyngeal swab, which is the preferred sampling method for respiratory viruses [7]. The assay typically targets the highly conserved 5' untranslated region (5' UTR) of the rinovirus genome, enabling broad detection across different genotypes [47]. Despite its accuracy, a key limitation is the cross-reactivity with enteroviruses, as both belong to the genus Enterovirus and share significant genetic similarity, which can complicate precise identification without additional sequencing [48].

RT-PCR offers significant advantages over older diagnostic methods. Unlike viral culture, which is slow (taking up to 7–10 days) and has low sensitivity due to the difficulty of growing rinovirus in cell lines, PCR provides results within hours and can detect the virus even at low viral loads or in asymptomatic individuals [109]. Similarly, rapid antigen tests are less sensitive and specific, making them unreliable for definitive diagnosis, especially in research or surveillance settings [110].

Clinical Contexts Requiring Laboratory Confirmation

Although most rinovirus infections are mild and self-limiting, molecular testing plays a critical role in specific clinical contexts where accurate diagnosis influences patient management. In patients with asthma, rinovirus is a leading trigger of acute exacerbations, particularly in children and adolescents [111]. Confirming the presence of the virus via PCR helps distinguish viral-induced worsening from other causes, guiding appropriate therapy and avoiding unnecessary use of antibiotics [112].

Similarly, in individuals with chronic obstructive pulmonary disease (COPD), viral infections including rinovirus are responsible for a significant proportion of acute exacerbations [113]. Identifying the pathogen through PCR allows clinicians to differentiate between viral and bacterial etiologies, optimizing treatment strategies and reducing inappropriate antibiotic prescriptions [65].

In immunocompromised patients or those with underlying lung disease, rinovirus can progress to lower respiratory tract infections such as bronchitis, bronchiolitis, or even pneumonia [115]. In these cases, laboratory confirmation is crucial for monitoring disease progression and implementing infection control measures. Moreover, during outbreaks or in hospital settings, multiplex PCR panels that simultaneously test for multiple respiratory pathogens—including rinovirus, influenza, SARS-CoV-2, and respiratory syncytial virus (RSV)—are invaluable tools for rapid differential diagnosis and effective public health response [116].

Role in Surveillance and Epidemiology

Beyond individual patient care, PCR-based testing is integral to national and international surveillance systems. In Italy, the RespiVirNet network, coordinated by the Istituto Superiore di Sanità (ISS), integrates clinical and virological data to monitor the circulation of respiratory viruses, including rinovirus, across the population [49]. This system enables timely detection of seasonal trends, co-circulation with other pathogens, and the emergence of new variants, providing critical information for public health planning [118].

Globally, while there is no centralized surveillance program for rinovirus managed by the World Health Organization (WHO), its circulation is tracked indirectly through integrated respiratory virus monitoring networks [63]. Environmental surveillance, such as wastewater analysis, has also emerged as a powerful tool for detecting viral prevalence and genetic diversity in communities, even in the absence of clinical symptoms [71].

Limitations and Future Directions

Despite the advantages of molecular diagnostics, challenges remain. The high genetic variability of rinovirus—over 160 known genotypes across species A, B, and C—can affect primer binding and reduce assay sensitivity if not properly accounted for in test design [26]. Additionally, the lack of standardized commercial assays and the need for specialized laboratory infrastructure limit widespread access in resource-limited settings.

Future improvements may include the development of more robust, pan-rhinovirus assays with enhanced coverage across all serotypes, as well as point-of-care molecular devices that deliver rapid results in outpatient clinics. Integration of diagnostic data with clinical outcomes through digital health platforms could further enhance the utility of testing in managing respiratory illnesses and preventing complications in vulnerable populations.

Management and Treatment

The management of rinovirus infections focuses on symptomatic relief, as no specific antiviral therapies or vaccines are currently approved for clinical use [2]. Given the virus’s role as the leading cause of the common cold, treatment strategies aim to alleviate discomfort, support recovery, and prevent complications, particularly in vulnerable populations such as infants, the elderly, and individuals with chronic respiratory conditions like asthma or chronic obstructive pulmonary disease (COPD) [5].

Symptomatic Relief and Supportive Care

Since rinovirus infections are typically self-limiting, lasting 7–10 days on average, treatment emphasizes supportive measures. Key recommendations include:

  • Rest and hydration: Adequate rest and fluid intake help maintain mucosal integrity and support the immune system in combating the virus [124].
  • Analgesics and antipyretics: Over-the-counter medications such as paracetamol (acetaminophen) or ibuprofen are effective for relieving headache, muscle aches, and low-grade fever, which are common in children [125].
  • Nasal decongestants: Topical or oral decongestants, such as pseudoephedrine or nasal sprays, can reduce nasal congestion and improve breathing [126].
  • Saline nasal irrigation: The use of saline sprays or rinses helps clear mucus and soothe irritated nasal passages, particularly in children [127].
  • Humidification: Using a humidifier in dry indoor environments can ease airway irritation and reduce coughing, especially during colder months [127].

It is important to note that antibiotics are ineffective against rinovirus, as it is a viral pathogen. Their use is not recommended unless there is strong evidence of a secondary bacterial infection, such as sinusitis or otitis media [129].

Role of Zinc and Other Supplements

Some evidence suggests that early administration of zinc may reduce the duration and severity of cold symptoms. Studies indicate that zinc lozenges or syrup, when started within 24–48 hours of symptom onset, can modestly shorten the illness by interfering with viral replication in the nasopharynx [124]. However, the benefits must be weighed against potential side effects, such as nausea or altered taste.

Other supplements, including vitamin C and echinacea, have shown inconsistent results in clinical trials and are not routinely recommended for treatment or prevention [5].

Management in High-Risk Populations

In individuals with preexisting respiratory conditions, rinovirus infections can trigger severe complications, necessitating more aggressive monitoring and intervention:

  • Asthma exacerbations: Rinovirus is a major trigger of acute asthma attacks, especially in children. Management includes early use of inhaled bronchodilators like salbutamol and, in severe cases, systemic corticosteroids to control airway inflammation [132]. The Global Initiative for Asthma (GINA) guidelines emphasize optimizing baseline asthma control to reduce vulnerability to viral triggers [133].
  • COPD exacerbations: In patients with chronic obstructive pulmonary disease, rinovirus-induced exacerbations may require increased bronchodilator therapy, corticosteroids, and sometimes hospitalization for oxygen support [134].
  • Immunocompromised patients: These individuals are at higher risk for prolonged or lower respiratory tract infections, including pneumonia. Close clinical monitoring and supportive care are essential, with consideration of antiviral research therapies in select cases [66].

Emerging Therapeutic Strategies

Despite the lack of approved antivirals, research is actively exploring targeted interventions:

  • Interferon-based therapies: Trials have investigated inhaled interferon-beta to boost the innate immune response, particularly in patients with impaired interferon production, such as those with asthma or COPD. While promising in theory, clinical benefits have been limited, possibly due to delayed administration [34].
  • Monoclonal antibodies: Inspired by the success of nirsevimab for respiratory syncytial virus (RSV) prevention, researchers are evaluating monoclonal antibodies targeting conserved epitopes on the rinovirus capsid, especially in high-risk pediatric populations [137].
  • RNA-based therapies: Novel approaches using small interfering RNA (siRNA) or antisense oligonucleotides aim to silence essential viral genes, offering a potential path for broad-spectrum antiviral development [138].

Pharmacological Challenges and Development Barriers

The development of antivirals has been hindered by several factors:

  • High serotype diversity: With over 160 identified serotypes across three species—rhinovirus A, rhinovirus B, and rhinovirus C—achieving broad-spectrum coverage is extremely difficult [28].
  • Rapid mutation rate: As an RNA virus lacking proofreading capability, rinovirus accumulates mutations quickly, increasing the risk of drug resistance [34].
  • Pharmacokinetic limitations: Past candidates like pleconaril and rupintrivir showed efficacy in vitro but failed in clinical trials due to poor bioavailability, toxicity, or insufficient delivery to respiratory tissues [141].

Preventive Measures and Public Health Implications

While not a direct treatment, prevention plays a critical role in reducing the burden of rinovirus infections. Key strategies include:

  • Hand hygiene: Frequent handwashing with soap and water or use of alcohol-based sanitizers reduces transmission via contaminated surfaces [142].
  • Respiratory etiquette: Covering the mouth and nose with a tissue or elbow during coughing and sneezing helps limit aerosol spread [2].
  • Surface disinfection: Regular cleaning of high-touch surfaces, such as doorknobs and phones, is crucial in schools, homes, and healthcare settings [2].
  • Vaccination against co-circulating pathogens: Although no rinovirus vaccine exists, annual influenza vaccination and pneumococcal vaccination can reduce the risk of co-infections and secondary complications [145].

In summary, the management of rinovirus infections remains primarily supportive, with a strong emphasis on symptom control and preventive practices. Ongoing research into antiviral agents, immunomodulators, and passive immunization offers hope for future therapeutic advances, particularly for high-risk individuals who suffer the greatest clinical consequences.

Role in Chronic Respiratory Diseases

The rinovirus plays a pivotal role in the exacerbation and progression of chronic respiratory diseases, particularly asthma and chronic obstructive pulmonary disease (COPD), acting as one of the most common viral triggers of acute worsening episodes. While typically associated with mild upper respiratory tract infections, in individuals with preexisting respiratory conditions, rinovirus infection can lead to severe clinical deterioration, increased healthcare utilization, and a significant burden on quality of life [146]. The virus is responsible for a substantial proportion of acute exacerbations, with epidemiological studies indicating that it accounts for approximately 60–80% of virus-induced asthma attacks in children and a significant share in adults [93]. This central role is formally recognized by international guidelines, including the Global Initiative for Asthma (GINA), which identifies rinovirus as a primary trigger for asthma exacerbations [133].

Exacerbations in Asthma

In patients with asthma, rinovirus infection is the leading cause of acute exacerbations, especially in pediatric populations. The virus triggers a cascade of inflammatory events that destabilize airway control, leading to increased bronchial hyperresponsiveness, mucus hypersecretion, and bronchoconstriction. This results in a rapid worsening of symptoms such as wheezing, cough, and shortness of breath, often necessitating emergency care or hospitalization [146]. The risk of exacerbation is particularly high when a rinovirus infection coincides with allergen exposure, as the dual insult amplifies the inflammatory response in the airways [93]. Furthermore, early-life infections, particularly with Rhinovirus C (RV-C), have been strongly linked to an increased risk of developing persistent asthma in childhood, suggesting a potential role not only in triggering acute episodes but also in the disease's pathogenesis [94]. A follow-up study found a high incidence of recurrent wheezing one year after a rinovirus-induced bronchiolitis, indicating a long-term impact on airway stability [152].

Exacerbations in Chronic Obstructive Pulmonary Disease (COPD)

Similarly, in chronic obstructive pulmonary disease (COPD), rinovirus is one of the most frequently identified viral pathogens during acute exacerbations. These episodes are critical events that accelerate the decline in lung function and increase mortality. Infections with rinovirus are associated with a significant worsening of dyspnea, cough, and sputum production, often leading to acute respiratory failure and hospital admission [153]. The management of such exacerbations requires prompt clinical assessment, including spirometry, pulse oximetry, and blood gas analysis, to evaluate the extent of functional impairment [134]. The presence of a viral trigger, as opposed to a bacterial one, is crucial for clinical decision-making, as it helps prevent the inappropriate use of antibiotics, which are ineffective against viral infections [113].

Immunopathogenic Mechanisms

The underlying immunopathogenic mechanisms that link rinovirus to the exacerbation of chronic respiratory diseases are complex and involve a dysregulated immune response. A key factor is the impaired innate antiviral response observed in patients with asthma and COPD. Their airway epithelial cells exhibit a reduced production of type I (IFN-β) and type III (IFN-λ) interferons, which are critical for controlling viral replication. This deficiency allows for higher and more prolonged viral loads, facilitating a more severe infection [33]. Concurrently, infected epithelial cells release "alarmin" cytokines such as IL-25, IL-33, and thymic stromal lymphopoietin (TSLP), which activate type 2 innate lymphoid cells (ILC2). This initiates a Th2-type inflammatory response, characterized by the production of IL-4, IL-5, and IL-13, leading to eosinophilic inflammation, bronchial hyperreactivity, and mucus overproduction—hallmarks of asthma [33]. The virus also promotes immune evasion by inducing the expression of immunosuppressive molecules like PD-1 on T cells and dendritic cells, leading to an ineffective immune response [158]. This combination of a weak antiviral defense and an exaggerated inflammatory reaction creates a perfect storm for airway damage and clinical deterioration.

Role of Different Rhinovirus Species

The three species of rinovirus—Rhinovirus A (RV-A), Rhinovirus B (RV-B), and Rhinovirus C (RV-C)—differ in their pathogenic potential. While all can cause the common cold, RV-A and especially RV-C are associated with more severe disease and a higher frequency of complications in chronic respiratory conditions. RV-C has emerged as the most pathogenic group, strongly linked to severe respiratory infections in children, including bronchiolitis and pneumonia, and is a major contributor to acute asthma and COPD exacerbations [44]. It is frequently found in episodes of severe pediatric asthma and in patients with poor baseline lung function, highlighting its clinical significance [46]. The enhanced pathogenicity of RV-C may be due to its efficient replication in the lower airways and its interaction with the CDHR3 receptor, which is more highly expressed in individuals with a genetic predisposition to asthma [19].

Clinical Implications and Management

The recognition of rinovirus as a major driver of exacerbations has important clinical implications for the management of chronic respiratory diseases. Prevention strategies are multifaceted and include optimal control of the underlying disease through regular use of inhaled corticosteroids and bronchodilators, annual influenza vaccination to reduce the risk of co-infections, and strict adherence to hygiene measures such as handwashing and respiratory etiquette during peak viral seasons [146]. Early monitoring of symptoms is crucial to enable prompt intervention, such as the use of systemic corticosteroids or intensified bronchodilator therapy, to prevent hospitalization [163]. Research into targeted immunomodulatory therapies, such as inhaled interferon-beta or monoclonal antibodies against TSLP (e.g., tezepelumab), shows promise for preventing virus-induced exacerbations, although these are not yet standard of care [34].

Prevention and Public Health Strategies

Preventing the spread of rinovirus infections and mitigating their public health impact remains a significant challenge due to the absence of a specific vaccine and the virus's extensive genetic diversity. With over 160 identified serotypes, the development of a universal vaccine has proven difficult, as immunity to one serotype does not confer protection against others [2]. Consequently, prevention strategies are primarily centered on non-pharmaceutical interventions that target the virus's primary transmission routes: respiratory droplets, aerosols, and contact with contaminated surfaces [4]. These measures are critical in reducing the burden of the common cold and preventing severe complications in vulnerable populations.

Hygiene and Behavioral Interventions

The cornerstone of rinovirus prevention is rigorous personal and environmental hygiene. Frequent handwashing with soap and water is one of the most effective methods to disrupt transmission, as the virus can survive for hours on surfaces like doorknobs, phones, and toys [55]. When soap and water are unavailable, alcohol-based hand sanitizers are a suitable alternative. Individuals are advised to avoid touching their eyes, nose, and mouth with unwashed hands, as this is a primary route for viral entry into the body [2].

Respiratory hygiene is equally important. Covering the mouth and nose with a tissue or the elbow when coughing or sneezing helps contain the release of infectious droplets into the environment [169]. Used tissues should be disposed of immediately, followed by handwashing. Maintaining physical distance from individuals who are sick, especially in crowded and poorly ventilated indoor settings like schools and offices, can significantly reduce the risk of exposure [170].

Environmental and Community-Based Strategies

Environmental disinfection plays a vital role in community settings. Regular cleaning and disinfection of frequently touched surfaces in homes, schools, and healthcare facilities can limit the virus's persistence in the environment. The virus's stability on inanimate surfaces makes this a crucial intervention, particularly during peak transmission seasons in the autumn and spring [52]. Promoting good ventilation in indoor spaces is another key strategy, as it helps to dilute and remove airborne viral particles, reducing the risk of aerosol transmission [172].

Public health education campaigns are essential for promoting these behaviors. By raising awareness about the importance of hygiene and respiratory etiquette, health authorities can foster a culture of prevention within communities. This is particularly important for protecting high-risk groups, such as neonates, children, the elderly, and individuals with preexisting conditions like asthma or chronic obstructive pulmonary disease (COPD) [98].

Surveillance and Epidemiological Modeling

Robust surveillance systems are critical for monitoring rinovirus circulation and informing public health responses. In Italy, the RespiVirNet system, coordinated by the Istituto Superiore di Sanità, integrates data from general practitioners, pediatricians, and reference laboratories to track the incidence of acute respiratory infections (ARI) and the prevalence of circulating respiratory viruses, including rinovirus [49]. This integrated surveillance provides real-time data on viral trends, helping to identify seasonal peaks and co-circulation with other pathogens like SARS-CoV-2 and influenza [69].

This data is used to feed mathematical models, such as the SIR model (Suscettibili–Infetti–Risolti), which simulate the dynamics of viral transmission in a population [72]. These models help predict epidemic peaks, estimate the basic reproduction number (R0), and evaluate the potential impact of public health interventions. For instance, models can assess how improved hand hygiene or increased ventilation might reduce transmission rates. This predictive capability allows health authorities to plan resource allocation, such as staffing in emergency departments, and to time public health messaging effectively.

Challenges and Future Directions

The primary challenge in prevention is the lack of a specific antiviral or vaccine. While research into broad-spectrum antivirals and multivalent vaccines is ongoing, none are currently approved for clinical use [34]. This underscores the continued reliance on behavioral and environmental strategies. Furthermore, the high rate of asymptomatic or mild infections contributes to silent transmission, making containment more difficult [56].

Future public health strategies may benefit from lessons learned in managing other respiratory viruses. The success of monoclonal antibodies for preventing severe disease from the virus respiratorio sinciziale (VRS), such as nirsevimab, suggests a potential pathway for developing similar prophylactic treatments for high-risk individuals facing rinovirus infection [179]. Additionally, the rapid development of antivirals like remdesivir for SARS-CoV-2 highlights the potential of targeting conserved viral enzymes, such as the RNA-dependent RNA polymerase, which could be a viable strategy for future rinovirus therapeutics [180]. Until such advancements are realized, public health efforts will continue to focus on empowering individuals with the knowledge and tools to prevent transmission through simple, effective hygiene practices.

References