A narrative review and expert opinion on immunity-targeted approaches in the management of viral upper respiratory tract infections

Abstract

Upper respiratory tract infections (URTIs) are among the most common diseases encountered in primary medical care. Recurrent URTIs (RURTIs) considerably affect patient health and quality of life. Recent evidence indicates that increased attention is being paid to symptom improvement in clinical practice. However, the therapeutic opportunities associated with using a vector for improving the immune status of patients remain underestimated. As the most common sources of URTI are viral infections, antiviral agents with the potential to enhance host immune responses can be considered auxiliary, effective, and safe for children and adults with URTIs and RURTIs. This review reports the current evidence and expert opinions on immunity-targeted approaches in the management of viral URTIs. Undelayed diagnosis and initiating treatment in the early stages of URTIs are crucial elements that can significantly improve disease evolution and the overall health of patients of any age group. An immunomodulatory remedy would be optimal for facilitating the healing of acute infections, reducing recurrence and complications, antibiotic consumption, and the consequences of antibiotic overuse. Maintaining and protecting the intestinal microbiota is also an important step toward effective URTI treatment. The findings of this review provide valuable insights into the effective management of URTIs and RURTIs based on the latest clinical evidence.

Introduction

Upper respiratory tract infections (URTIs), such as rhinitis, laryngitis, pharyngitis, and nasopharyngitis, are among the most widespread diseases in primary medical care¹. The primary causes of URTIs are viruses, including multiple strains of rhinovirus, influenza virus, coronavirus, adenovirus, respiratory syncytial virus, and enterovirus².

Each respiratory virus elicits a distinct immune response, influenced by its unique structural and functional characteristics. Figure 1 presents a comparative analysis of the immune responses elicited by the influenza virus, respiratory syncytial virus (RSV), and SARS-CoV-2.

Fig. 1. Comparative analysis of the immune responses elicited by the influenza virus, respiratory syncytial virus (RSV), and SARS-CoV-2.

PRR Pattern Recognition Receptor, TLR Toll-Like Receptor, RIG-I Retinoic acid-Inducible Gene I, IFN Interferon, NK cells Natural Killer cells, Th2 T-helper 2 cell, CD4⁺ T cells Cluster of Differentiation 4 positive T cells (helper T cells), CD8⁺ T cells Cluster of Differentiation 8 positive T cells (cytotoxic T cells), RSV Respiratory Syncytial Virus, SARS-CoV-2 Severe Acute Respiratory Syndrome Coronavirus 2/, B cells B lymphocytes (antibody-producing cells)^32–37.

Approximately 200 viral strains cause URTI, with viral incubation usually lasting two to four days. Bacterial colonization can follow a viral infection, aggravating the disease and resulting in a lengthened recovery period and evolution with complications³.

The most prevalent symptoms of URTIs are cough, sore throat, nasal obstruction, fever and headache. Despite such conditions being mainly self-limiting and nonfatal, the accompanying symptoms can cause significant impairment to one’s productivity and quality of life³. Recurrent respiratory tract infections (RRTIs) are typical clinical conditions in adults and children^3,4.

URTIs are more prevalent during winter months, as the causative pathogens are transmitted either via aerosolized droplets or contaminated secretions, which can subsequently invade one’s eyes or the respiratory epithelium⁵. Crowded places, such as schools or daycare facilities, are therefore favorable environments for transmitting respiratory pathogens^5,6.

Considering the widespread effects of URTIs on the well-being and quality of life of adults and children around the world, a narrative review and expert opinion on approaches to their management is warranted. In the present review, a multinational group of experts in the field of viral infections of the respiratory tract has investigated these diseases and proposed treatments that may reduce the negative clinical and monetary impact of URTIs on children, adults, and society.

Recurrent respiratory infections

Recurrent respiratory infections in children

Recurrent respiratory infections are common in children. Nearly 25% of children experience RRTIs during their first year of life and approximately 6% of children under 6 years of age experience RRTIs⁴. In most cases, these infections pass with mild symptoms and the frequency of infection tends to reduce over time, with a complete resolution typically around 12 years of age. Nonetheless, RRTIs can significantly negatively impact the quality of life of the child and family and have important medical and social costs⁴. In some cases, URTIs can cause acute complications such as otitis media, pneumonia, glomerulonephritis, and myocarditis³.

There is a lack of universal consensus on the definition of RRTIs⁷. A consensus was published proposing an up-to-date definition and recommendations to guide physicians in the complex process of diagnosing, managing, and preventing pediatric RRTIs. For example, childhood respiratory tract infections (RTIs) are considered recurrent if within a year a child aged 6–12 years has three or more RTIs (one of which can be pneumonia, including severe pneumonia) or two mild cases of pneumonia confirmed by X-rays and/or clinical criteria⁸.

The widespread presence of recurrent URTIs is not considered a global phenomenon. However, several cohort studies have attempted to estimate the prevalence of recurrent URTIs. The prospective, observational birth cohort study Steps to the Healthy Development and Well-being of Children (STEPS) observed 1,089 children from their birth until they turned 2 years old, tracking RTIs using a daily symptom diary. Recurrent RTIs were defined as more than 98 days of respiratory illness per year and was reported in 10% of the participant cohort. Approximately 60% of the participants with RRTIs were diagnosed with a minimum of three episodes of acute otitis, 73% received at least three courses of antibiotic treatment and 21% had been hospitalized with an acute form of RTI. By the time the children turned 2 years old, 12% had been diagnosed with asthma. Therefore, the authors concluded that RRTIs are a risk factor for asthma in children⁹.

There are a variety of factors that can cause an increased prevalence of RRTIs in younger children. As young children’s immune system is still relatively immature, they are more susceptible to RRTIs than healthy adults. For example, humoral and cellular immunity do not reach maturity until 5 or 6 years of age and an infant’s immune system has immature immune cell function and activation along with a Th2 cytokine imbalance⁸. In addition, increased exposure to infectious agents during the first few years of life, particularly when children attend preschool or school facilities and are exposed to groups of people, and environmental and social factors such as family size, parental smoking, air pollution, and household dampness, can all contribute to a higher prevalence of RRTIs⁷.

Recurrent respiratory infections in older adults

Older adults are particularly susceptible to severe viral respiratory infections. Potential explanations for this include immunosenescence, malnutrition, comorbidities (especially diabetes), polypharmacotherapy, treatment of certain comorbidities, and inflammatory conditions¹⁰. Immunosenescence refers to the changes in the immune system during the process of aging, which includes the decline of the efficiency and reliability of the immune system as well as a reduction in responsiveness-impaired communication between cells of the immune system¹¹. These alterations result in a higher risk of developing pathological conditions due to chronic inflammatory responses and enhanced vulnerability to infectious disease¹¹. Immunosenescence has a multifactorial etiology: for the acquired immune system, it involves the thymus and a decreased responsiveness to new antigens. This imbalance results in a diminished capacity to eliminate new pathogens, leading to prolonged infections. For the innate immune system, immunosenescence is primarily characterized by a decline in cellular superoxide production and phagocytic ability¹¹.

Upper respiratory tract infections in at-risk patients

Besides children and older adults, pregnant women, people with chronic medical conditions (such as chronic cardiac, renal, pulmonary, metabolic, liver, neurodevelopmental or hematologic diseases), and those with immunosuppressive conditions (such as HIV, malignancy or receiving chemotherapy/steroids) are also more susceptible to developing a more serious URTI or having an increased number of associated complications (for the possible effects of viral infections on patients with impaired immunity, see Fig. 2)¹². These at-risk groups are briefly reviewed in turn.

Fig. 2.

Evolution of viral URTIs.

Patients with a pre-existing metabolic and cardiovascular disease, specifically hypertension and coronary heart disease, are at a higher risk of developing severe and fatal upper and lower viral respiratory tract diseases¹². Diabetic patients are up to a 50% more likely to suffer fatal outcomes from upper and lower viral respiratory tract diseases than those without diabetes¹³.

Healthcare workers also have a high risk of contracting influenza virus infections as they are constantly exposed to patients, which can further spread to particularly vulnerable individuals¹².

Excess weight is another risk factor for RTIs¹³. Epidemiological studies have shown evidence that being overweight and obese is not only associated with a higher prevalence of RTIs but also longer disease duration and higher mortality rates^14–17. Both upper and lower respiratory tract infections are more prevalent among obese subjects and weight gain appears to increase the risk of RTIs¹³.

The alteration of the immune system may explain these increased rates of RTIs associated with excess weight. Obesity has been shown to have considerable effects on the immune system, possibly due to the structural and functional similarities between adipocytes and immune system cells, which can both produce mediators such as chemokines, cytokines, and adipokines¹³. ‘Low-grade inflammation’ can arise when excess adipose tissue is assimilated into a state of chronic inflammation, causing cell necrosis and dysfunction locally on the adipose tissue itself and altering the immune response at a systemic level¹⁸.

Managing recurrence and complications in URTIs

Current strategies for the management of acute URTI aim to alleviate symptoms and prevent the transmission of URTI viruses. Early intervention, administered before the peak of viral shedding, can drastically increase the effectiveness of these strategies. This decreases the likelihood of a full-blown acute URTI developing, reduces the severity of symptoms and viral transmission⁶.

Recurrent respiratory infections constitute a significant challenge from both therapeutic and preventive perspectives because of their effect on quality of life and medical and social expenditures⁴. Firstly, it is crucial to determine whether RRTIs are caused by host-derived or environmental factors. Recently, as antibiotic resistance has increased, interest in treatments with preventive approaches has also increased. These treatments should be capable of preventing RRTIs, thereby reducing the use and unreasonable consumption of antibiotics¹⁹.

Although antimicrobials play a major role in medicine, their use is becoming increasingly common, especially when administered as a preventive measure. The efficacy of antibiotics is reduced by the rapid emergence of resistant bacteria¹⁹. Therefore, reducing the use of antibiotics is a top priority among healthcare authorities worldwide to avoid the subsequent effects of overuse, such as increased antibiotic resistance and impairment of the mucosal microbiome¹⁹. Several alternative treatment options to antibiotics use will now be reviewed.

Microbiota

Microbiota play a key role in the introduction, training, and functioning of the host immune system. In response, the immune system has evolved to maintain a symbiotic relationship between the host and the highly diverse and evolving microbes²⁰.

At optimal operation, this alliance of the immune system and microbiota induces pathogen-protective responses and the upkeep of regulatory pathways associated with maintaining and tolerating innocuous antigens^20,21.

If the gut microbiota is modified by an increase in the use of antibiotics, the severity of viral respiratory infections such as influenza increases. In contrast, the opposite effect is expected when the microbiome is stimulated by a diet high in fiber²¹.

Immunity-targeted approaches

A successful immune reponse to viral infections involves a complex interplay between both innate and adaptive immunity-related cell types²². The body’s first line of immune defense is the innate immune defense, in which natural killer (NK) cells, a type of innate lymphoid cells, play an important role. In response to stimuli from infections, cytokines, stress, and other immune cells, the NK cells rapidly and directly kill infected cells via three distinct actions. Firstly, they secrete perforin and granzymes to directly kill target cells. Then, they release cytokines to regulate the immune response. Lastly, they induce apoptosis by coupling with receptors on the target cells²³. Thus, NK cells can kill virus-infected cells without antigen presentation or recognition.

The second line of immune defense is adaptive immunity based on antigen presentation²². Antigen-presenting cells (APCs) process the virus and the most important antigens are displayed on the APC surface, along with molecules of the major histocompatibility complex. When a virus replicates inside a cell, the immune system identifies it to be a thymus-dependent intracellular antigen, causing the activation of adaptive immunity via T-helper 1 (Th1) cells and cytotoxic T-lymphocytes (CTLs). CTLs are similar to NK cells in terms of their cytotoxic activity. In addition, cytokines IL-2, TNF-α, and INF-γ are released which activate T-cells, dendritic cells and macrophages. When these two lines of immunity become overwhelmed (e.g., in cases of influenza or coronavirus infections), the virus is released into the blood, leading to viremia. Since the virus is then mostly extracellular, thymus-dependent extracellular antigen and T-helper 2 (Th2) cells are activated. Th2 cells, along with T follicular helper cells (Tfh), stimulate antibody production. These antibodies then mark viral particles for destruction by macrophages by binding to the extracellular antigens on viral cells (for summary on immunity-targeted approaches in viral upper respiratory tract infections, see Fig. 3)²².

Fig. 3. Overview of immunity-targeted approaches in viral upper respiratory tract infections (URTIs)²⁹.

APC Antigen-Presenting Cell, MHC Major Histocompatibility Complex, CTL CD8+ Cytotoxic T-Lymphocytes, Tfl T follicular helper cell, IgA, IgG Immunoglobulin A and G, URTIs Upper Respiratory Tract Infections, NK Natural Killer, NKG2D Natural Killer Group 2D, Th T-helper cell, IL Interleukin, IFN Interferon, TNF Tumor Necrosis Factor.

In the immune system, there is an important balance between Th1 and Th2 cell activity²². When Th1 activity increases as part of innate immunity, Th2 activity is suppressed by Th1 cytokines, and vice versa. The immune system activity is alike the pendulum of a clock that, depending on the stimulus and type of antigen, swings from one side (Th1 stimulated by thymus-dependent intracellular antigens) to the other (Th2 stimulated by thymus-dependent extracellular antigens). Both Th1 and Th2 activity cannot be activated simultaneously²².

Immunomodulators or immune enhancers can be used to improve or influence a patient’s innate immune response²⁴. These drugs are effective and can be used in conjunction with vaccines⁵. Immune enhancers positively affect long-term patient outcomes by preventing further infections²². Preventive strategies are the foundation of the clinical management of RRTIs as they offer a mechanism for interrupting the vicious cycle of microbial infection, the reappearance of mucosal inflammation due to the interaction between microbes and the first-line immune defense of the host, and a malfunctioning immune response⁸. As opposed to vaccines, which have an immunity-stimulating effect against a specific antigen, immune enhancers induce a general state of ‘pre-alert’ in the host and enhance the overall immune response²⁴.

Strategies capable of rebalancing immunity are also the current focus of the medical and research community, as equilibrium between the branches of the immune system is necessary for the coordination between the phases of activation and repression to precisely identify, process, and eliminate pathogens²⁴. An example product in this context is OM-85, a drug with an immunomodulatory effect that has proven to be effective in improving the health conditions of patients suffering from frequent URTI recurrences. OM-85 is a lysate of 21 bacterial pathogen strains derived from eight major species and subspecies that commonly cause RTIs and is the most studied immunomodulating agent for preventing infection^24,25. Multiple studies have shown that OM-85 can act on both innate and adaptive immunity. Firstly, OM-85 induces dendritic cell maturation in gastrointestinal Peyer’s patches, which in turn increases the immune defenses in the lung mucosa²⁶. In addition to this, OM-85 treatment can reduce tissue damage by controlling inflammation in the presence of chronic inflammatory conditions, such as chronic rhinosinusitis, by decreasing pro-inflammatory cytokines (e.g., IL-1b)²⁷ and increasing anti-inflammatory cytokines (e.g., IL-10)²⁸. Thus, OM-85 effectively induces the early activation of the immune system, resulting in a balanced release of anti-inflammatory cytokines and factors that provide early protection against infections and a control over inflammation²⁴. In this way, OM-85’s nonspecific effect on the immune system enhances its natural defense against infection and weakens respiratory tract inflammation caused by infections and allergens. Therefore, OM-85 bacterial lysate represents a possible strategy for managing RRTIs caused by viruses and bacteria in at-risk individuals²⁴. Multiple studies support this claim. A randomized, placebo-controlled study demonstrated the efficacy of OM-85 in reducing recurrent infections in children. Additional research has shown its immunomodulatory effects in pediatric populations with recurrent upper respiratory tract infections (RURTIs), along with mechanistic evidence supporting its action on dendritic cells and mucosal immune responses.

• Schaad UB et al.: A multicenter, randomized, placebo-controlled trial demonstrating the efficacy of OM-85 in reducing recurrent infections in children (Chest. 2002;122(6):2042-2049. 10.1378/chest.122.6.2042).

• Esposito S et al.: A double-blind, placebo-controlled study confirming OM-85’s ability to modulate immune responses in pediatric patients with RURTIs (J Transl Med. 2019;17:284. 10.1186/s12967-019-2017-3).

• Pilette C et al.: A mechanistic study highlighting OM-85’s stimulation of dendritic cells and mucosal immunity (Am J Respir Crit Care Med. 2001;164(8 Pt 1):1459–1464. 10.1164/ajrccm.164.8.2103011).

Inosine

The nucleoside inosine is a microbiota-derived metabolite essential for purine biosynthesis and degradation²³. It acts as a bioactive molecule that regulates RNA editing, metabolic enzyme activity, and signaling pathways, subsequently materializing as a multifaceted bioactive substance and acting as a second messenger of signal transduction in cells with various functional abilities in diverse pathological states²³.

Inosine enhances immunotherapeutic results and antitumor T-cell feedback²³. Various microbes inhabiting the intestinal microbiota have been proposed to produce inosine, indicating their therapeutic efficacy in diverse disease models, e.g., alcohol-induced liver injury, dextran sulfate sodium-induced colitis, or indomethacin-induced enteropathy²³. Recent studies have pinpointed the critical connection between the gut microbiota and inosine-induced initiation of anti-inflammatory, antitumor and antimicrobial responses, depending on context²³.

Inosine pranobex (IP) is a drug formed by inosine with dimepranol acedoben (acetamidobenzoic acid and dimethylaminoisopropanol)²³. IP is well known for its positive effects in modulating and balancing immune parameters in patients with impaired immunity, as well as its direct antiviral effect on DNA and RNA viruses. IP, commonly known as inosine acedoben dimepranol, isoprinosine, or methisoprinol, was first authorized in 1971, and is currently marketed for the treatment of viral diseases in over 70 countries²².

IP is used to treat a variety of infections, such as acute viral respiratory infections, subacute sclerosing panencephalitis, herpes simplex infections, measles, varicella, and infections caused by human papillomavirus, Epstein-Barr virus and cytomegalovirus²². Previous studies have shown that the immunomodulatory activity of IP is mediated by increased lymphocyte proliferation, NK cell cytotoxicity and cytokine production (for a detailed description on the mechanism of action of IP on the different immune components, see Fig. 4)²². Over the last five years, IP has been confirmed to be effective and safe for treating most investigated viral infections, including acute respiratory viral infections, as observed in clinical and immunological studies²². Findings reveal that the immunomodulatory properties are sourced from metabolic activation with natural killer group 2D (NKG2D) ligand induction. The latest findings that IP has a boosting effect on phenotypically competent NK cells in healthy individuals support the proposed benefits of the drug in viral infections and strengthen the compromised immune performance²².

Fig. 4. Immunity-Targeted Mechanisms of Inosine Pranobex in Viral Upper Respiratory Tract Infections (URTIs)³⁸.

URTIs Upper Respiratory Tract Infections, IP Inosine Pranobex, NK Natural Killer, NKG2D Natural Killer Group 2D, Th T-helper cell, IL-2 Interleukin-2, IFN Interferon, TNF Tumor Necrosis Factor.

Discussion

URTIs continue to be a major reason for doctor’s visits and missing school and workdays, which lead to a decrease in quality of life and financial losses³. The evolution through repeated occurrences and complications can result in the URTI turning into a condition with a high possibility for aggravation and a highly negative effect on the individual’s quality of life⁹. Regardless of the main causative agents of URTI being viruses, such conditions cause most cases of antibiotic use and overuse⁵.

Children, older adults, and those with health conditions characterized by autoimmune diseases, diabetes, obesity, multimorbidity, immunosuppressive treatments, and sedentary lifestyle are at a considerably higher predisposition to URTI development with recurrences and complications^5,24. For children, the most common causes include immature immunity levels, low weight at birth, and attending crowded preschool and school institutions⁵. In the case of older adults, immunosenescence, alongside several other factors, form a web of causes predisposing them to recurrent URTIs and their aggravation^10,24.

Vaccination as a cornerstone in the prevention and mitigation of viral upper respiratory tract infections

Vaccination remains a keystone in the prevention and mitigation of viral upper respiratory tract infections (URTIs). By stimulating the immune system to recognize and combat specific pathogens, vaccines not only reduce the incidence of infections but also lessen the severity of disease outcomes. The primary strength of vaccination lies in its ability to prevent severe illness and death. While vaccines may not entirely prevent infection, they are effective in reducing the severity of symptoms and the risk of complications. Moreover, vaccination contributes to herd immunity, indirectly protecting unvaccinated individuals by reducing the overall circulation of pathogens. This is particularly important in the context of URTIs, which are highly contagious and can lead to significant morbidity, especially among vulnerable populations such as the elderly, young children, and individuals with chronic health conditions. In addition to individual protection, widespread vaccination can alleviate the burden on healthcare systems by reducing the number of severe cases requiring medical attention. This is crucial during peak seasons of respiratory infections when healthcare resources are often stretched thin. Furthermore, by decreasing the incidence of severe disease, vaccination can reduce the need for antibiotic prescriptions, thereby contributing to the fight against antibiotic resistance²⁹.

Limitations of current vaccination strategies for upper respiratory tract infections

While vaccination is a cornerstone in preventing URTIs, several limitations hinder its comprehensive efficacy. One significant constraint is the limited induction of mucosal immunity by traditional intramuscular vaccines. These vaccines primarily stimulate systemic immune responses but may not elicit robust immunity at mucosal surfaces, such as the nasal and pharyngeal mucosa, which are primary entry points for respiratory pathogens. This limitation can result in reduced effectiveness in preventing initial infection and transmission of respiratory viruses³⁰. Additionally, the specificity of vaccines to pathogens means they may not protect against the wide array of viruses responsible for URTIs. For instance, while vaccines exist for influenza and SARS-CoV-2, there are currently no approved vaccines for common URTI-causing viruses like rhinoviruses and certain coronaviruses. This gap leaves individuals susceptible to infections from these prevalent pathogens. Furthermore, vaccine efficacy can be compromised in certain populations. Elderly individuals and those with immunocompromising conditions often exhibit diminished immune responses to vaccination, leading to lower levels of protection. This is particularly concerning given that these groups are at higher risk for severe outcomes from URTIs. These limitations underscore the need for complementary strategies to enhance protection against URTIs³¹.

Prompt diagnosis and treatment of URTIs are vital components that have a significant impact on the evolution of diseases and overall health conditions in patients of all age groups³. Receiving an immunity enhancer with an antiviral effect early has the potential to not only reduce the risk of recurrence and complications, but also help reduce antibiotic consumption²². Any reasonable solution that can result in a reduction in antibiotic consumption among the population is considered favorable¹⁹. To tackle this growing resistance, it is vital to use antibiotics appropriately at the necessary times, including the use of suitable dose intervals and for the relevant duration¹⁹.

Therapeutic approaches targeted at improving and modulating immunity are appropriate not only for the effective treatment of persisting infections of the upper respiratory tract but also for the prevention of recurrence and upcoming complications⁸. The use of antibiotics in an irrational manner not only leads to antibiotic resistance but may also have negative and even occasionally irreversible effects on the intestinal microbiota²¹. Maintaining and protecting the intestinal microbiota and avoiding its alteration are crucial steps toward effective URTI treatment²³.

Immunomodulation needs to be discussed as it holds the potential of preventing the development of severe viral infections alongside their complications, primarily relating to microbial infections, as demonstrated in randomized clinical trials evaluating its preventive efficacy in populations with recurrent respiratory infections²⁶. This consensus paper has its strengths and limitations. The main strength of the present paper is that a board of international experts reviewed existing clinical literature and formulated a list of consensus statements that are scientifically and clinically relevant and valid. Additionally, the diverse clinical backgrounds of the expert group was another strength of this review, as the clinicians’ expertise provides reliability to the consensus provided. The recommendations by this review are valuable as they have the potential to guide clinicians in their daily clinical practice to optimize treatment and thereby likely improve outcomes. The limitations of this review are that we reviewed and summarized a specific number of studies, no complete Cochrane-type literature search or AI analysis was performed. Furthermore, no animal experiments or in vitro studies were reviewed.

Conclusions and recommendations

Viral URTIs considerably affect the health status and quality of life of patients of any age as well as their families, owing to physiological changes, frequent medical visits, school/work absenteeism, antibiotic overuse, bacterial resistance, weakening of lung function, greater risk of asthma development, and financial burden.

Identifying those at risk of recurrence and complications (such as patients with chronic pulmonary, cardiovascular or metabolic diseases, children and older adults) and prompt management can have a positive impact on a patient’s well-being and financial welfare. Any reasonable solution that can result in the reduction of antibiotic consumption among the population is indisputably important; using antibiotics only when needed and respecting the indicated dose and regimen are vital for tackling growing antibiotic resistance.

Considering a remedy with the potential to modulate a patient’s immunity is reasonable to facilitate the healing of acute infections, decrease recurrence and complications, antibiotic consumption, and the global consequences of antibiotic overuse. IP, an antiviral remedy with immunomodulatory properties, is a safe and effective adjunctive treatment for patients with impaired immunity and recurrent infections in the upper part of the respiratory tract. The further collection of information on “inosine through IP as stabilizing microbiotic agent” based on the latest publications and data from potential present-day studies can be beneficial for both scientific discussions in the medical community, as well as transforming prescription patterns.

Methodology

This narrative review and expert opinion paper is based on a comprehensive review of the literature combined with the clinical experience and interpretation of the contributing authors, who are recognized experts in infectious diseases, immunology, and respiratory medicine. A literature search was conducted using PubMed, Scopus, and Web of Science databases, covering publications from January 2010 to March 2025. Keywords included ‘upper respiratory tract infections’, ‘immunomodulation’, ‘innate immunity’, ‘inosine pranobex’, and ‘recurrent URTIs’. Studies were selected based on relevance, scientific quality, and applicability to immunity-targeted strategies. In addition, reference mining of key articles ensured comprehensive coverage. The findings represent a synthesis of current evidence and expert clinical judgment.

Author contributions

Conceptualization, J.B., R.K., P.J. and L.T.; methodology, J.B., R.K., P.J. and L.T.; writing—original draft preparation, J.B., R.K., P.J. and L.T.; writing—review and editing, J.B., R.K., P.J. and L.T.; project administration, L.T. All authors have read and agreed to the published version of the manuscript.

Data Availability

No new data were created or analyzed in this study. Data sharing is not applicable to this article.

Competing interests

The authors declare no competing interests.