Acute respiratory viral infections (ARVI) in adults: clinical guidelines

List of Abbreviations

WHO – World Health Organization

Dr. Med. Sci. – Doctor of Medical Sciences

DNA – deoxyribonucleic acid

VLE – List of Vital and Essential Drugs

Cand. Med. Sci. – Candidate of Medical Sciences

CT – computed tomography

Ministry of Health of the Russian Federation – Ministry of Health of the Russian Federation

ICD-10 – International Statistical Classification of Diseases and Related Health Problems 10th Revision

INN – International Nonproprietary Name

NSAIDs – nonsteroidal anti-inflammatory drugs

CHI – Compulsory Health Insurance

ARVI – Acute respiratory viral infections

ICU – intensive care unit

RF – Russian Federation

FL – Federal Law

Terms and Definitions

Evidence-based medicine – an approach to medical practice in which decisions about the use of preventive, diagnostic, and therapeutic measures are made based on available evidence of their efficacy and safety, and such evidence is searched for, compared, summarized, and widely disseminated for use in the best interests of patients.

Disease – a disturbance of bodily function, working capacity, and the ability to adapt to changing environmental conditions arising from the impact of pathogenic factors, accompanied by alterations in the body's protective-compensatory and protective-adaptive reactions and mechanisms.

Primary disease – a disease that, by itself or due to complications, necessitates primary medical care due to the greatest threat to working capacity, life, and health, or leads to disability, or causes death.

Concomitant disease – a disease that has no causal relationship with the primary disease, is secondary to it in terms of the need for medical care, impact on working capacity, danger to life and health, and is not the cause of death.

Severity of a disease or condition – a criterion determining the degree of damage to human organs and/or body systems or the impairment of their functions caused by a disease or condition or their complication.

Disease outcomes – the medical and biological consequences of a disease.

Consequences (outcomes) – disease outcomes, social and economic results of the application of medical technologies.

Disease complication – the addition to a disease of a physiological process disturbance syndrome; – disruption of the integrity of an organ or its wall; – hemorrhage; – developed acute or chronic failure of the function of an organ or organ system.

Instrumental diagnostics – diagnostics performed by examining a patient using various devices, apparatuses and instruments.

Quality of medical care – a set of characteristics reflecting the timeliness of medical care, the correctness of the choice of prevention, diagnosis, treatment, and rehabilitation methods during the provision of care, and the degree of achievement of the planned result.

Clinical guidelines – a document based on proven clinical experience that describes the physician's actions regarding the diagnosis, treatment, rehabilitation, and prevention of diseases, helping them make correct clinical decisions.

Laboratory diagnostics – a set of methods aimed at analyzing the test material using various specialized equipment.

Patient model – a set of clinical, laboratory, and instrumental diagnostic signs that allow identifying a disease (poisoning, trauma, physiological state) and classifying it into a group of conditions with a common etiology and pathogenesis, clinical manifestations, general approaches to treatment and condition correction.

Medical worker – an individual who has a medical or other education, works in a medical organization and whose labor (job) duties include the implementation of medical activities, or an individual who is an individual entrepreneur, directly.

Nosological form – a set of clinical, laboratory, and instrumental diagnostic signs that allow identifying a disease (poisoning, trauma, physiological state) and classifying it into a group of conditions with a general etiology and pathogenesis, clinical manifestations, general.

Syndrome – a condition developing as a consequence of a disease and defined by a set of clinical, laboratory, and instrumental diagnostic signs that allow identifying it and classifying it into a group of conditions with a different etiology, but a common pathogenesis, clinical manifestations, general approaches to treatment, which, however, also depend on the diseases underlying the syndrome.

Level of evidence certainty – reflects the degree of certainty that the found effect of a medical intervention is true.

Grade of recommendation – reflects not only the certainty in the reliability of the intervention's effect, but also the certainty that following the recommendations will bring more benefit than harm in a specific situation.

Drug formularies – a fragment of patient treatment protocols containing information on medications used for a specific disease (syndrome), regimens, and specifics of their prescription.

1. Brief information on the disease or condition

1.1 Definition of the disease or condition

Acute respiratory viral infections (ARVI) – a group of infectious diseases of viral etiology transmitted by airborne droplets and proceeding with predominant damage to the upper, less often lower respiratory tracts with localization of the pathogen in them.

Clinical guidelines for some specific ARVI pathogens (for example, type A and B influenza viruses, new coronavirus infection – SARS-CoV-2) are set out in separate documents and are not considered in these guidelines.

1.2 Etiology and pathogenesis of the disease or condition (group of diseases or conditions)

The most common ARVI pathogens are respiratory syncytial virus (RSV) A and B, respiratory enterovirus (EV), rhinovirus (RV), adenovirus (ADV), human metapneumovirus (hMPV), parainfluenza virus (PIV) types 1 to 4, and seasonal coronaviruses (CoV–NL63, OC43, HKU-1, and 229E). Respiratory viruses are mainly RNA-containing [1, 2]. Diseases caused by the above pathogens share common mechanisms and transmission routes, pathogenesis stages, and clinical manifestations.

Main stages of pathogenesis:

• adhesion and invasion into respiratory epithelial cells and its reproduction;

• development of intoxication syndrome and toxic-allergic reactions;

• development of an inflammatory process in various parts of the respiratory tract;

• formation of immunity;

• pathogen elimination;

• recovery.

The nature of the infectious process course is determined by a complex system of protective and adaptive reactions of the macroorganism aimed at limiting viral reproduction and their elimination.

The mucous membrane of the upper respiratory tract serves as the entry gate, and the epithelium is the first barrier to the penetration of viruses into the human body. The mucus layer effectively protects, and mucociliary clearance removes viral particles from the respiratory epithelium.

At the initial stage of infection development, nonspecific defense factors play a leading role – interferons, secretory IgA antibodies, and phagocytosis; during recovery – specific and humoral immunity. IgA prevents the adhesion of pathogens to the epithelial cell surface, mediating the destruction and elimination of viruses. In case of failure of local defense mechanisms, viruses primarily affect the cells of the cylindrical epithelium of the respiratory tract with the further development of subsequent stages of pathogenesis [2].

Damage to target cells by respiratory viruses leads to their destruction, phagocytosis by macrophages, infiltration of the epithelial layer by mononuclear cells – producers of endogenous proinflammatory cytokines (interleukins, tumor necrosis factor-alpha, interferons, etc.), as well as leukotrienes, enzymes, oxygen radicals, etc. Both local inflammation and intoxication syndrome are formed [2].

Next, cytolysis of infected epitheliocytes occurs, which is carried out due to the action of antigen-specific cytotoxic lymphocytes, natural killers, and specific IgM antibodies. This leads to the destruction of affected cells and the release of cellular breakdown products from them. Endogenous biologically active substances and cellular breakdown products penetrate the blood, which also contributes to the development of intoxication syndrome [2].

Local inflammatory changes and intoxication vary in severity depending on the specific etiological agent.

The cytotoxic action of lymphocytes, macrophages, and specific antibodies leads to the elimination of the pathogen with the formation of specific humoral and cellular immunity. Reparative processes occur in parallel in the mucous membranes of the affected sections of the respiratory tract, and local homeostasis normalizes.

An increase in regional lymph nodes is possible, as well as a systemic reaction – the involvement of the mononuclear phagocyte system organs in the pathological process – enlargement of the liver and spleen (in adenovirus infection). The development of allergic reactions of the body with the formation of toxic-allergic reactions in the form of exanthema is noted [2].

General pathomorphological changes in ARVI:

• cytoplasmic and intranuclear destruction of epithelial cells;

• impairment of the functional activity and integrity of cilia and, consequently, mucociliary clearance, which is also a local defense factor;

• in a number of cases, dystrophic changes in the epithelium and the possible appearance of serous or serous-hemorrhagic exudate in the alveolar lumen.

During and after a past ARVI, local and general immunity is depleted, immunosuppression is formed, and the weakened body becomes vulnerable to other pathogens – viruses and bacteria.

1.3 Epidemiology of the Disease or Condition

ARVI account for a significant share (90–95%) of the overall structure of infectious morbidity in the population. In the Russian Federation (RF), the number of annual cases exceeds 30 million people [2, 3, 5]. On average, adults experience 2 to 4 recurrent ARVI episodes annually. Severe courses and fatalities are observed in various ARVI, mostly as an outcome of ADV, PIV, and RSV infections, occurring both as mono- and mixed infections [5, 6]. ARVI is associated with 30–50% of community-acquired pneumonia cases [7, 8, 9, 10]. The seasonal rise in morbidity occurs from September to May. ARVI are aerogenic anthroponoses. The source is patients with clinically pronounced or mild/subclinical forms of the disease, as well as those in the prodromal period. The primary transmission mechanism is aerosol, while contact-fomite and fecal-oral routes are likely in some cases [1, 2, 3].

1.4 Features of Coding the Disease or Condition

International Statistical Classification of Diseases and Related Health Problems (10th Revision):

J00 – Acute nasopharyngitis [common cold]

J01 – Acute sinusitis

J02 – Acute pharyngitis

J03 – Acute tonsillitis

J04 – Acute laryngitis and tracheitis

J05 – Acute obstructive laryngitis [croup] and epiglottitis

J06 – Acute upper respiratory infections of multiple and unspecified sites

J20 – Acute bronchitis

J21 – Acute bronchiolitis

J22 – Unspecified acute lower respiratory infection

B34.0 – Adenoviral infection, unspecified

B34.2 – Coronavirus infection, unspecified, other than that caused by COVID-19

B34.9 – Viral infection, unspecified

B97.0 – Adenoviruses as the cause of diseases classified in other chapters

B97.4 – Respiratory syncytial virus as the cause of diseases classified in other chapters

1.5 Classification of the disease or condition

A. By clinical course:

1. Typical (manifest);

2. Atypical (asymptomatic, mild/subclinical).

B. By severity:

1. Mild;

2. Moderate;

3. Severe;

4. Very severe.

C. By the nature of the course:

1. Uncomplicated;

2. Complicated (specific complications, complications caused by secondary microflora, exacerbation of chronic diseases).

D. By duration:

1. Acute (5–10 days);

2. Subacute (11–30 days);

3. Protracted (more than 30 days).

1.6 Clinical presentation of the disease or condition

The incubation period for ARVI ranges from 1 to 14 days (from 1 to 5 days for the most common viruses).

The disease typically begins gradually with the onset of a moderate intoxication syndrome (low-grade or high-grade fever, general malaise, headache, muscle and joint pain), as well as catarrhal (catarrhal-respiratory) syndrome — sore throat, cough, rhinorrhea, and in some cases conjunctivitis. Development of lymphoproliferative syndrome is possible, manifested by lymphadenopathy, and less frequently hepatomegaly (adenoviral infection).

Despite the similarity of the clinical picture, different causative agents have varying tropism for sections of the respiratory tract, which determines the specific symptoms. Appendix A3 presents the clinical characteristics of the main respiratory tract lesion syndromes, the main causative agents of ARVI, the clinical syndromes they cause, and the severity grades of ARVI [1, 2, 13].

Complications of acute respiratory viral infections are subdivided into specific and secondary, caused by the activation of secondary microflora.

Specific complications: meningism, acute respiratory failure, encephalopathy, infectious-toxic shock — acute vascular failure, adult respiratory distress syndrome, acute cardiovascular failure, myocarditis, thromboembolism.

Complications caused by activation of secondary bacterial microflora: acute sinusitis, acute otitis media, acute bronchitis, exacerbation of chronic bronchopulmonary diseases, pneumonia [1, 2, 6].

2. Diagnostics, medical indications and contraindications for diagnostic methods

Diagnostic criteria

Diagnosis of ARVI in adults is based on complaints, anamnestic data, clinical examination, laboratory, instrumental, and special diagnostic methods, and is aimed at determining the nosology and clinical form, severity of the condition, identifying complications and indications for therapy.

2.1 Complaints and Anamnesis

Comments: such factors may include drug hypersensitivity; inadequate psychoemotional state of the patient prior to treatment; a life-threatening acute condition/disease or exacerbation of a chronic disease requiring the involvement of a relevant medical specialist; refusal of treatment.

2.2 Physical Examination

Comments: identifying catarrhal symptoms is mandatory at the initial stage of ARVI diagnosis. However, the above symptoms may also be a manifestation of certain bacterial infections, in particular streptococcal or meningococcal nasopharyngitis [19, 23].

2.3 Laboratory Diagnostics

2.3.1. Nonspecific laboratory diagnostics

Comments: viral infections in a complete blood count are typically characterized by leukopenia or normocytosis, lymphocytosis, and monocytosis.

Comments: in an uncomplicated course of acute respiratory viral infection (ARVI), there are no pathological changes; in case of pronounced fever or intoxication syndrome, there is an increase in urine specific gravity, mild transient leukocyturia, proteinuria, and cylindruria, which disappear upon normalization of body temperature and relief of general infectious intoxication symptoms.

2.3.2. Specific laboratory diagnostics

Comments: use of the rapid immunochromatographic assay (ICA) method for the detection of influenza A and B virus antigens, respiratory syncytial virus, adenovirus, and SARS-CoV-2 coronavirus in nasopharyngeal swabs in patients seeking medical care no later than 2 days from the onset of symptoms.

Comments: molecular biological testing of nasopharyngeal and oropharyngeal swabs for SARS-CoV-2 coronavirus, molecular biological testing of nasopharyngeal swabs for influenza virus (Influenzavirus), determination of influenza A virus (Influenzavirus A) and influenza B virus (Influenzavirus B) RNA in nasopharyngeal swabs by PCR, determination of parainfluenza virus (Human Parainfluenzavirus), rhinovirus (Human Rhinovirus), respiratory syncytial virus (Human Respiratory Syncytialvirus), metapneumovirus (Human Metapneumovirus) RNA in oropharyngeal swabs by PCR, determination of rhinovirus (Human Rhinovirus) RNA in nasopharyngeal swabs by PCR, determination of adenovirus (Human Adenovirus) DNA in oropharyngeal swabs by PCR, molecular biological testing of oropharyngeal swabs for 229E, OC43, NL63, HKUI coronaviruses (Human Coronavirus) and bocavirus (Human Bocavirus) — determination of viruses most frequently causing upper and lower respiratory tract infections for differential diagnosis, in order to prescribe etiotropic therapy for the timely prevention of severe disease development and complications. In case of suspected lower respiratory tract disease, an examination of sputum, tracheal or pharyngeal aspirates, and bronchoalveolar lavage fluid is performed. This is the most effective method that allows the detection of viral nucleic acids on average up to 7 days, and at most up to 2 weeks from the onset of the disease (provided that signs of upper respiratory tract involvement persist). Results are obtained within 4–6 hours after sample submission.

2.4 Instrumental Diagnostics

Comments: pulse oximetry is a simple and reliable screening method that allows identifying patients with hypoxemia who need respiratory support and assessing its effectiveness.

GR CLEL 5Grade of Recommendation C (Level of Evidence – 5).

Comments: according to observations, this complication occurs in 0.5–2% of ARVI cases in adults. At the same time, the presence of pathological changes in the paranasal sinuses does not always confirm the development of bacterial involvement [29].

2.5 Other Procedures

2.5.1 Differential diagnosis [1, 2, 6, 15, 19, 20, 22, 23, 35, 72, 88]

It is necessary to carry out a differential diagnosis of respiratory viral etiology and bacterial acute respiratory infections (ARI), including viral and bacterial pneumonia.

Differential diagnosis of ARVI is presented in Appendix A3.

3. Treatment, including drug and non-drug therapies, diet therapy, and pain management

The principles of treatment for patients with ARVI involve addressing the following tasks:

• suppression of viral replication in the early stages of the disease (antiviral therapy);

• prevention of the further development of the pathological process caused by the disease, and achievement of complete and stable recovery;

• prevention of possible complications of the disease.

The choice of treatment tactics is influenced by the following factors [1, 2, 3, 5, 13, 19, 23, 26, 27, 65, 88]: period of the disease; severity of the disease; clinical form of the disease; leading clinical manifestations and features of the disease course taking into account signs of immunodeficiency (chronic alcoholism, emaciation, severe comorbid pathology, old age); patient's age; presence and nature of complications; availability and feasibility of treatment in accordance with the required type of medical care.

Information regarding doses, indications for use, and routes of administration of medicinal products contained in these guidelines may differ from the information specified in the package leaflet (PIL). For complete information on the use of a particular medicinal product, the PIL should be consulted. Personal responsibility for the interpretation and use of these guidelines rests with the attending physician.

3.1. Conservative management

3.1.1. Etiotropic (antiviral therapy)

Comments: prescribed depending on the etiology. Early administration of antiviral drugs for acute respiratory viral infections (ARVI) to suppress viral replication prevents the development of severe disease and reduces the risk of complications. The advisability of prescribing antiviral drugs is determined by the physician individually for each patient. Regimens and dosages are detailed in the treatment section of the clinical guidelines: "Influenza in Adults" and the interim guidelines "Prevention, Diagnosis, and Treatment of the Novel Coronavirus Infection (COVID-19)" version 18 [9–12].

Comments: riamilovir exhibits a broad spectrum of antiviral activity against RNA viruses by inhibiting viral RNA synthesis and genomic fragment replication. The active substance is a synthetic analogue of purine nucleoside (guanine) bases. Treatment should be initiated no later than the 2nd day after the onset of clinical symptoms: orally, regardless of food intake, 1 capsule (250 mg) 3 times a day (total daily dose – 750 mg) for 5 days.

- Umifenovir** [6, 27, 28, 39, 40, 52, 53, 62].

AG CLEL 2Recommendation Grade C (Level of Evidence – 2).

Comments: Umifenovir** specifically inhibits influenza A and B viruses in vitro (Influenzavirus A, B), including highly pathogenic subtypes A(H1N1)pdm09 and A(H5N1), as well as other ARVI pathogens (severe acute respiratory syndrome [SARS]-associated coronavirus [Coronavirus], rhinovirus [Rhinovirus], adenovirus [Adenovirus], respiratory syncytial virus [Pneumovirus], and parainfluenza virus [Paramyxovirus]). In vitro studies have shown it specifically inhibits the SARS-CoV-2 virus causing the novel coronavirus infection (COVID-19). The recommended administration schedule is a single dose of 200 mg 4 times a day (every 6 hours) for 5 days.

Contraindicated in hypersensitivity to the drug components and during the first trimester of pregnancy. Umifenovir** may be used for ARVI prior to laboratory confirmation of diagnosis in suspected COVID-19 cases, in accordance with the interim guidelines "Drug Therapy for Acute Respiratory Viral Infections (ARVI) in Outpatient Practice During the COVID-19 Epidemic" (version 2). Following diagnostic confirmation, treatment is conducted in accordance with these clinical guidelines for ARVI treatment or the interim guidelines for COVID-19 treatment [72], under which umifenovir** is used to treat mild forms of COVID-19 (200 mg 4 times/day for 5–7 days).

- Enisamium iodide [6, 44, 45, 45, 68, 69].

AG CLEL 2Recommendation Grade C (Level of Evidence – 2).

Comment: inhibits the action of influenza viruses and other ARVI pathogens through a direct (inhibitory) effect on viral penetration across the cell membrane. It possesses interferonogenic properties, increasing blood plasma concentrations of endogenous interferon (interferon alfa and interferon gamma) by 3 to 4 times.

The recommended dosage regimen is 500 mg 3 times a day orally for a course of 5–7 days. Contraindicated in hypersensitivity to the drug components, lactase deficiency, lactose intolerance, glucose-galactose malabsorption, sucrase/isomaltase deficiency, fructose intolerance, pregnancy and breastfeeding, a history of allergic reactions, and severe organic liver and kidney lesions.

Comments: the mechanism of action of imidazolylethanamide pentanedioic acid** is implemented at the level of infected cells by stimulating innate immunity factors that are suppressed by viral proteins. The drug enhances the expression of interferon receptors on the cell membrane. It increases blood interferon levels to the physiological norm and exhibits anti-inflammatory activity.

The recommended dosage regimen is 90 mg once daily regardless of food intake, with a treatment duration of 5–7 days depending on the severity of the condition. It is advisable to start treatment no later than two days from the onset of the disease. Contraindicated in hypersensitivity to the drug components, pregnancy, lactation, lactase deficiency, lactose intolerance, and glucose-galactose malabsorption.

- Meglumine acridone acetate** [6, 11, 54, 55, 56, 95–98].

GGR BLOC 1Grade of Recommendation B (Level of Evidence – 1).

Comments: is an interferon inducer, which determines its wide spectrum of biological activity (antiviral, immunomodulatory, anti-inflammatory, etc.). It is effective against the influenza virus and other acute respiratory infection pathogens. It possesses direct antiviral action, suppressing viral reproduction in the early stages (days 1–5) of the infectious process, reducing the infectivity of viral progeny, and leading to the formation of defective viral particles. It increases the body's nonspecific resistance to viral and bacterial infections. The recommended treatment schedule for ARVI is 4 tablets as a single dose on days 1, 2, 4, 6, and 8 (20 tablets total). Contraindicated in hypersensitivity to the drug components, pregnancy, and lactation.

- Oxyethylammonium methylphenoxyacetate [102–109].

GCR CLOE 5Grade of Recommendation C (Level of Evidence – 5).

Comments: exhibits immunomodulatory, antiviral, and adaptogenic effects. It is an interferon inducer. It stimulates the body to produce interferons (alfa, gamma), exerts a direct stimulating effect on B-lymphocyte proliferation and enhances the production of lymphokines and monokines, stimulates macrophage phagocytic activity, and activates immunoglobulin A (IgA) synthesis. The adaptogenic effect is associated with optimizing energy production and expenditure, enhancing RNA and protein synthesis in major body organs and systems, increasing endurance under physical and mental stress, mitigating the effects of various toxins, and increasing the body's resistance to hypoxia, low and high temperatures, and other adverse environmental factors. It is not included in the list of drugs recommended by international clinical guidelines for influenza treatment and prevention. Administered orally: for treatment, 200 mg 3 times a day on the first day, followed by 200 mg once a day for the next 7 days (total course dose of 2000 mg); for prevention: 200 mg daily (total course dose of 2800 mg). Contraindicated in hypersensitivity to the drug components, pregnancy, lactation, children under 12 years of age, hereditary lactose intolerance, lactase deficiency, or glucose-galactose malabsorption.

- Azoximer bromide** [115–123].

GCR CLOE 5Grade of Recommendation C (Level of Evidence – 5).

Comments: exhibits pronounced immunomodulatory activity (leads to enhanced T-cell proliferation and stimulates dendritic cell maturation with the expression of co-stimulatory molecules and increased antibody production, ensures the activation of cytokine production, enhances the production of interleukins and interferon-alfa, and increases NK cell cytotoxicity indices), and exerts a nonspecific protective effect against a wide range of pathogens based on the regulation of macroorganism immunity. Additionally, the drug exhibits antitoxic and antioxidant properties.

Tablets: 1 tablet sublingually 2 times a day for 7 days.

Solution: parenterally 6 mg daily for 3 days, then every other day for a total course of 10 injections, or intranasally or sublingually 6 mg daily, with the daily dose (6 mg) administered in 2–3 divided doses per day.

Suppositories: 12 mg suppositories once daily. Course of treatment: 10 suppositories.

Contraindicated in hypersensitivity to the drug components, pregnancy, and breastfeeding.

- Tilorone** [6, 193–196].

Level CLevel 5Level of recommendation evidence C (reliability level of evidence – 5).

Comments: interferon inducer. Stimulates the body to produce all types of interferons (alfa, beta, gamma, and lambda), enhances antibody production, reduces the degree of immunosuppression, and restores the T-suppressor to T-helper ratio. Exhibits immunomodulatory and antiviral effects. Used as part of combination therapy. The recommended dosage regimen for the treatment of influenza and ARVI is 125 mg daily for the first 2 days of treatment, then 125 mg every 48 hours. Course dose – 750 mg (6 tablets). Contraindicated in hypersensitivity to the drug components, pregnancy, lactation, and children under 18 years of age.

- Ergoferon (affinity-purified antibodies to human gamma interferon – 10,000 RELEASE, affinity-purified antibodies to histamine – 10,000 RELEASE, affinity-purified antibodies to CD4 – 10,000 RELEASE) [6, 76–78, 193].

AG CLEL 2Recommendation Grade C (Level of Evidence – 2).

Comments: the drug has antiviral, immunomodulatory, anti-inflammatory, and antihistamine effects; it can be prescribed as monotherapy or in combination with other antiviral, antibacterial, pathogenetic, and symptomatic agents.

On the 1st day of treatment, 8 tablets are taken according to the following schedule: 1 tablet every 30 minutes for the first 2 hours (5 tablets total in 2 hours), then another 1 tablet 3 times at equal intervals during the rest of the day. On the 2nd day and thereafter, 1 tablet is taken 3 times a day until complete recovery.

Not applicable in congenital galactosemia, glucose-galactose malabsorption syndrome, or congenital lactase deficiency. The efficacy and safety of the drug have not been studied in pregnant women and during lactation.

- Rafamin (affinity-purified antibodies to human interferon gamma – 10,000 EMD, affinity-purified antibodies to CD4 – 10,000 EMD, affinity-purified antibodies to MHC class I β2-microglobulin – 10,000 EMD, affinity-purified antibodies to MHC class II β1-domain – 10,000 EMD) [79, 80].

Level of Evidence BLevel of Confidence 2Level of recommendation B (level of evidence – 2).

Comments: the drug exhibits antiviral, antibacterial, and anti-inflammatory activity. When used concomitantly with antibiotics, it enhances the efficacy of antibiotic therapy, including against resistant pathogen strains, and helps preserve normal intestinal microflora. It can be used as monotherapy or in combination with other antiviral, antibacterial, pathogenetic, and symptomatic agents in patients with ARVI over 18 years of age.

Orally according to the schedule: on the 1st day of treatment – 8 tablets – 1 tablet every 30 minutes for the first 2 hours (5 tablets total in 2 hours), then another 1 tablet 3 times at equal intervals during the rest of the day. On the 2nd day and thereafter, 1 tablet is taken 3 times a day. The duration of treatment is 5 days. Not applicable in congenital galactosemia, glucose-galactose malabsorption syndrome, or congenital lactase deficiency. The efficacy and safety of the drug have not been studied in pregnant women and during lactation.

Comments: Interferon alfa-2b and human recombinant interferon gamma**, administered intranasally, have an indirect antiviral effect on ARVI viruses. With intranasal administration, the concentration of the active substance achieved in the blood is not clinically significant. They are used in combination therapy regimens for ARVI at the first signs of the disease. They are not included in the list of medicines recommended by international clinical guidelines for the treatment and prevention of ARVI.

Interferon alfa-2b is prescribed intranasally, 3 drops/doses in each nasal passage 5–6 times a day (single dose – 3,000 IU, daily dose – 15,000–18,000 IU) for 5 days;

Human recombinant interferon gamma**. Prescribed intranasally, 2 drops in each nasal passage after cleansing the nasal passages, 5 times a day for 5–7 days.

Comments: Bacterial lysates [Haemophilus influenzae + Klebsiella ozaenae + Klebsiella pneumoniae + Moraxella catarrhalis + Staphylococcus aureus + Streptococcus pneumoniae + Streptococcus pyogenes + Streptococcus viridans] are a systemically acting drug that enhances the mucosal immune response to both viral and bacterial infection in the respiratory tract by increasing the efficiency of innate and adaptive immunity mechanisms. The use of bacterial lysates [Haemophilus influenzae + Klebsiella ozaenae + Klebsiella pneumoniae + Moraxella catarrhalis + Staphylococcus aureus + Streptococcus pneumoniae + Streptococcus pyogenes + Streptococcus viridans] in the combination therapy of ARVI helps reduce disease duration and symptom severity. It is prescribed from the first days of the disease: 1 capsule per day in the morning on an empty stomach, 30 minutes before meals until symptoms disappear, but for at least 10 days [130–136, 191].

3.1.2. Pathogenetic and symptomatic therapy

Comments: basic therapy includes bed rest, diet, and adequate fluid intake. The diet should include easily digestible foods rich in vitamins (lean meats, fish, dairy products, fruits, vegetables, juices, stewed fruit). Alcohol in any form is strictly prohibited.

The organization of medical nutrition for patients with ARVI during inpatient treatment in medical organizations is carried out in accordance with the orders of the Russian Ministry of Health dated August 5, 2003 No. 330 "On measures to improve medical nutrition in medical and preventive institutions of the Russian Federation", dated June 21, 2013 No. 395n "On approval of medical nutrition standards" and dated September 23, 2020 No. 1008n "On approval of the procedure for providing patients with medical nutrition".

Comments: the volume depends on the patient's severity degree.

Mild and moderate severity at the outpatient stage of treatment – oral detoxification in the volume of 2–3 liters of fluid per day (weakly brewed tea with milk, honey, jam, as well as rosehip decoction, freshly prepared fruit and berry juices, compotes, alkaline mineral waters).

Moderate severity during inpatient treatment – oral detoxification and/or infusion therapy: 800–2000 ml using B05BB Blood substitutes and perfusion solutions / Solutions affecting the electrolyte balance.

Duration is determined by the severity of the intoxication syndrome.

In complicated and severe courses of ARVI – intravenous detoxification with correction of electrolyte disturbances: using complex solutions B05BB Solutions affecting the electrolyte balance. Volume and duration depend on the patient's severity degree.

Comments: administered intravenously by drip at a rate of 1-4.5 ml/min (up to 90 drops per minute). The average daily dose is 10 ml/kg. The course of therapy is up to 11 days. The volume and duration depend on the severity of the patient's condition.

Comment: the use of NSAIDs is possible only for symptomatic purposes to achieve antipyretic and analgesic effects. Prescribing them as a long-term course is inappropriate. In addition, from a practical standpoint, it should be remembered that prescribing NSAIDs may disorient the physician in evaluating the efficacy of ongoing therapy.

– Drugs of choice: paracetamol** 1–2 tablets (500–1000 mg) every 4–6 hours, as needed. Maximum daily dose: 4,000 mg (8 tablets), ibuprofen** 400 mg 3 times daily (maximum daily dose – 1200 mg), combination dosage forms: paracetamol in combination with other drugs, except psycholeptics: Ibuprofen + Paracetamol (200 mg + 500 mg) [130, 137, 138], Paracetamol + Phenylephrine + Pheniramine [36, 37, 50, 51, 93].

Comments: Xylometazoline**. Intranasal. Recommended dose: 1–2 drops (1 puff) 3 times a day; Naphazoline – intranasally (into each nasal passage) 1–3 drops of 0.05–0.1% solution 3–4 times a day;

In case of excessive rhinorrhea, a fixed combination of Ipratropium Bromide + Xylometazoline may be used;

Oxymetazoline – intranasally (into each nasal passage), 1–2 drops of 0.05% solution, 1–2 puffs into each nasal passage 2 times a day.

GPP CLOE 4Grade of Recommendation C (Level of Evidence – 4).

Comments: for treatment from the first day of the disease as baseline therapy with pronounced secretolytic, secretomotor, and anti-inflammatory effects, all patients with symptoms of nasopharyngitis and/or rhinosinusitis may be prescribed combined herbal preparations containing gentian root, primrose flowers, sorrel herb, elderberry flowers, and vervain herb (ATC code: R05X, R07AX).

Combined herbal preparations containing gentian root, primrose flowers, sorrel herb, elderberry flowers, and vervain herb (ATC code: R05X, R07AX):

Dry native extract (Sinupret Extract) 160 mg (1 tab.) 3 times a day for 7–14 days.

Comminuted herbal raw material (Sinupret tablets) 156 mg (2 tabs.) 3 times a day for 7–14 days.

Water-alcohol extract (Sinupret drops) 50 drops 3 times a day for 7–14 days.

Pregnant patients with symptoms of common cold/nasopharyngitis and acute rhinosinusitis, after consulting a physician, may be prescribed combined herbal preparations containing gentian root, primrose flowers, sorrel herb, elderberry flowers, and vervain herb (ATC code: R05X) in the form of film-coated tablets or oral drops if tablets cannot be used.

Comments: local antiseptics are used: Gramicidin S + Cetylpyridinium chloride, Gramicidin S + Oxybuprocaine + Cetylpyridinium chloride, Benzydamine + Cetylpyridinium chloride, Flurbiprofen + Cetylpyridinium chloride, hexetidine, lysozyme + pyridoxine, chlorhexidine**, Benzyldimethyl-myristoylamino-propylammonium, biclotimol, iodine preparations, Benzyldimethyl [3-(myristoylamino)propyl] ammonium chloride monohydrate.

Comments: a medicinal product containing marsh mallow root, chamomile flowers, yarrow herb, oak bark, walnut leaves, horsetail herb, and dandelion herb (ATC code: R02AA20) (Tonsilgon N, ATC code: R02AA20) has demonstrated high pharmacological efficacy in patients with pharyngitis and tonsillitis, as it possesses proven immunomodulatory, antiseptic, antibacterial, antiviral, and anti-inflammatory effects.

A medicinal product containing marsh mallow root, chamomile flowers, yarrow herb, oak bark, walnut leaves, horsetail herb, and dandelion herb (ATC code: R02AA20):

Comminuted herbal raw material (Tonsilgon N tablets) 96 mg (2 tabs.) 5–6 times a day until acute symptoms (sore throat) disappear, then for another week 96 mg (2 tabs.) 3 times a day (long-term course use is possible).

Liquid extract (Tonsilgon N drops) 25 drops 5–6 times a day until acute symptoms (sore throat) disappear, then for another week 25 drops 3 times a day (long-term course use is possible).

This herbal medicinal product may also be prescribed to pregnant women and patients with somatic diseases after consulting a physician.

Comments: drugs of choice are:

Dextromethorphan (part of multi-component drugs); (Dextromethorphan + Paracetamol + Phenylephrine + Chlorphenamine, Dextromethorphan + Paracetamol + Pseudoephedrine, Dextromethorphan + Terpin hydrate + [Levomentol], Dextromethorphan + Phenylephrine + Chlorphenamine

Ascorbic acid + Dextromethorphan + Paracetamol + Pseudoephedrine)

Butamirate – orally, 15 ml 4 times a day (syrup).

Levodropropizine – orally, between meals, for adults and children over 12 years – 60 mg (10 ml of syrup or 20 drops, preferably diluted in half a glass of water) 1–3 times a day at intervals of at least 6 hours.

Rengalin, 1–2 tablets or 5–10 ml of oral solution 3 times a day independently of meals. Depending on the severity of the condition, the frequency of administration in the first three days can be increased to 4–6 times a day. The duration of therapy depends on the severity of the disease and is determined by the attending physician. Not applicable in hereditary fructose intolerance. The efficacy and safety of the drug have not been studied in pregnant and lactating women [81-83].

Comments: various mucolytic agents, including herbal medicinal products, can be used only in the presence of a productive cough.

Synthetic mucolytic agents:

Acetylcysteine** – orally 600 mg/day, course up to 5–7 days [130, 153, 154];

Bromhexine – orally 8 mg 3 (1–2 tablets) 3–4 times a day;

Ambroxol** – orally 90 mg/day, prolonged-release capsules 75 mg/day, course up to 14 days;

Ambroxol + Sodium Glycyrrhizinate + Creeping Thyme Herb Extract – orally 40 ml/day (10 ml in 4 doses).

Ambroxol + Sodium Bicarbonate + Sodium Glycyrrhizinate + Lanceleaf Thermopsis Herb Extract, 1 tablet 3 times a day.

Natural mucolytic agents: combined herbal medicinal products from the group of expectorants (ATC code R05CA10, Expectorants in combination) containing fixed combinations of liquid extracts of thyme and ivy (English Ivy Leaf Extract + Thyme Herb Extract, syrup, ATC code R05CA10), dry extracts of thyme and primrose (Primrose Root Extract + Thyme Herb Extract, ATC code R05CA10). These combinations have proven efficacy in the treatment of acute bronchitis, possess a comprehensive effect: expectorant, anti-inflammatory, secretolytic, bronchodilator, and contribute to reducing sputum viscosity and accelerating its evacuation similarly to synthetic mucolytic agents, while having better treatment tolerability [36, 37, 155-159].

English Ivy Leaf Extract + Thyme Herb Extract (syrup) – 5.4 ml 3 times a day after meals for 10–14 days.

Primrose Root Extract + Thyme Herb Extract, 1 tablet 3 times a day before meals for 10–14 days.

Comments: nebulized inhalations: Ingasalin® 3%: hypertonic solution (sodium chloride – 30 mg) with sodium hyaluronate (0.1 mg) or Ingasalin Forte® 7%: hypertonic solution (sodium chloride – 70 mg) with sodium hyaluronate (1.0 mg), one ampoule (5 ml) 2 times a day or according to the physician's prescription. Treatment can be started with a lower amount and the dose increased gradually.

Comments: the combination of ipratropium bromide + fenoterol** in the form of a metered-dose inhaler (MDI) at a dose of 20 mcg/dose + 50 mcg/dose — 1–2 puffs up to 3–4 times daily, or as a solution for nebulizer inhalation at a dose of 0.25 mg/ml + 0.5 mg/ml (1–2 ml) up to 3–4 times daily.

Comments: used as an oral solution, 10 ml 3 times a day for 2 weeks.

Antibacterial drugs

Comment: the drugs of choice for bacterial rhinosinusitis are:

• Amoxicillin** — 500–1000 mg 3 times a day, orally, course of 7–10 days.

• Amoxicillin + [Clavulanic acid]** — 1 tablet (500 mg + 125 mg) 3 times a day or 1 tablet (875 mg + 125 mg) 2 times a day, orally, course of 7–10 days.

• Azithromycin** — 500 mg, once daily orally, 3-day course.

• Clarithromycin** — 500 mg (once daily), course of 7–10 days.

• Levofloxacin** — 500 mg, orally, course of up to 5–7 days (for bacterial infections caused by microflora resistant to other antibiotics, in case of treatment failure with other antibacterial agents, and in the presence of a history of exanthem or drug allergy to other antibiotics).

Treatment of pneumonia is not covered in these guidelines and is carried out in accordance with the clinical guidelines for the management of community-acquired pneumonia in adults!

Comments: treatment in this case will be carried out in accordance with the clinical guidelines for emergency conditions in an intensive care unit!

Comments: if signs of respiratory failure appear (SpO₂ < 92%), it is necessary to provide oxygen inhalation via nasal catheters or face masks. Depending on the clinical situation (degree of hypoxemia, response to oxygen therapy), various delivery systems are used to supply oxygen to the patient's airways: nasal cannulas (allow generating an oxygen-air mixture with an FiO₃ of up to 24–40%); a standard face mask (FiO₄ 35–50%); or high-flow nasal cannula (HFNC) therapy. Start with a medium flow rate (5–7 L/min), increasing up to 10 L/min if necessary to ensure an acceptable level of blood oxygenation (PaO₅ greater than 60 mm Hg, SpO₆ above 90%).

Other drugs

Comments: recommended dose: 20 mg of omeprazole once daily.

Comments: probiotics are prescribed as part of complex therapy in the early stages of ARVI. The use of agents regulating the balance of the intestinal microflora (probiotics) in combination with antiviral, antibacterial drugs, or other pathogenetic agents is permitted.

• Single-component sorbed bifidobacterium bifidum probiotic** (2–3 capsules or 2–3 sachets 2 times a day for 7–10 days) [130, 164-170].

• Bifidobacterium bifidum + Lactobacillus plantarum (1 capsule or sachet) 3 times daily. Course — 5–10 days [130, 164-170].

• Linex Forte (combination of Lactobacillus acidophilus (LA-5) and Bifidobacterium animalis subsp. lactis (BB-12)), 1–3 capsules daily depending on symptom severity [171-176].

• Bifidobacterium longum + Enterococcus faecium (2–3 capsules daily for 10–21 days);

• Saccharomyces boulardii (1–2 capsules twice daily during antibiotic use) [177, 178, 192].

3.2. Surgical treatment

Not performed.

4. Medical Rehabilitation and Sanatorium-Resort Treatment

Comments: oxyethylammonium methylphenoxyacetate possesses both immunomodulating and adaptogenic properties. Orally, 3 tablets (600 mg) per day on the first day, and 1 tablet (200 mg) for the subsequent 7 days. Total course dose is 10 tablets (total dose 2000 mg), course duration is 8 days [102-109, 190].

Comments: gradual increase in dosed physical and mental loads, as well as the differentiated application of various intervention methods, is important.

Comments: the speed and degree of recovery of the functional state and professionally significant functions of convalescents are taken into account (using indirect and direct methods).

5. Prevention and Dispensary Observation

5.1. Specific prophylaxis

Specific vaccine prophylaxis for acute respiratory viral infections has not been developed [1, 2, 3, 7, 19, 23, 72].

5.2. Nonspecific prevention 2

Comments: The patient is isolated at home or, if necessary, in a hospital setting in a separate box until complete clinical recovery (on average for 1–2 weeks). After clinical recovery, the patient is permitted to return to work. Outbreak control measures are not carried out. It is necessary to provide the patient with separate tableware and care items. Quarantine and isolation measures for contacts are not organized.

Comments: Non-specific prophylaxis is divided into two types: emergency prophylaxis, designed for the immediate antiviral effect of chemical drugs, interferons, and interferon inducers (intra-outbreak and extra-outbreak (scheduled)), and seasonal prophylaxis, carried out during the pre-epidemic period to increase the human body's resistance to respiratory viruses during the period of maximum probability of disease. Intra-outbreak prophylaxis is carried out among individuals who have been in direct contact with patients in families, apartments, or hospital wards (epidemiologic foci). The duration of intra-outbreak prophylaxis ranges from 2 days when contact with the source of infection ceases to 5–7 days if contact persists. Extra-outbreak prophylaxis is carried out among populations with an increased risk of ARVI infection and a high risk of adverse disease outcomes [1, 2, 3, 7, 23, 72].

Comments: in patients with chronic respiratory diseases, the use of Bacterial lysates [Haemophilus influenzae + Klebsiella ozaenae + Klebsiella pneumoniae + Moraxella catarrhalis + Staphylococcus aureus + Streptococcus pneumoniae + Streptococcus pyogenes + Streptococcus viridans] reduces the number of acute respiratory infection episodes and exacerbations of chronic disease, as well as the need for antibacterial therapy. It is prescribed in three 10-day courses, with an interval of 20 days between courses [130, 131, 134].

Comments: The efficacy against influenza A and B viruses, parainfluenza, rhinovirus, respiratory syncytial virus, adenovirus, seasonal coronavirus strains, metapneumovirus, and herpes simplex virus types 1 and 2 (labial herpes, genital herpes) has been established experimentally and clinically. For prophylactic purposes, the drug is taken as 1 tablet once a day for 1–3 months. It is contraindicated in case of hypersensitivity to the components of the drug, lactase deficiency, hereditary galactose intolerance, glucose-galactose malabsorption. The safety of use in pregnant and lactating women has not been studied. If necessary, the drug can be combined with other antiviral, antibacterial, and symptomatic agents.

Comments: A low vitamin D level is associated with an increased frequency of seasonal respiratory infections and a long-term deterioration in lung function indicators in adults. Intake ranges from 6 months to a year, in individuals without obesity (BMI < 30 kg/m²) at a dose of 2000 IU/day or 10,000 IU/week, and in the presence of obesity (BMI > 30 kg/m²) at higher doses from 3000 IU/day to 6000 IU/day. Long-term administration of A11CC05 #Cholecalciferol** is associated with the need to maintain its target level (30–60 ng/ml) throughout the year [180–184].

_____________________________________________________________________________

² _{Resolution of the Chief State Sanitary Doctor of the Russian Federation No. 4 dated January 28, 2021, "On the Approval of Sanitary Rules and Norms SanPiN 3.3686-21 'Sanitary and Epidemiological Requirements for the Prevention of Infectious Diseases'."}

5.3 Clinical follow-up (dispensary observation)

Comment: for medical services during outpatient monitoring for disease treatment (if necessary), condition assessment, and treatment monitoring, see Appendix A3.5.

• After discharge, for 1 month, it is recommended to refrain from routine vaccinations, except for (if indicated) tetanus toxoid** and rabies vaccine [1, 2].

GCR CLOE 5Grade of Recommendation C (Level of Evidence – 5).

6. Organization of Medical Care

The choice of treatment tactics is influenced by the following factors [1, 2, 3, 15, 34, 72]: patient's age; nature of comorbidities; clinical form of the disease; pattern of the disease course (dynamics of symptom progression); disease severity; presence and nature of complications.

Comment: risk groups for an adverse disease course are described in section 7.

Comments: 1) with symptoms indicating impaired oxygen supply to the body or cardiopulmonary failure (shortness of breath (upon exertion or at rest), labored breathing, cyanosis, bloody or colored sputum, chest pain, hypotension; hypoxia determined by pulse oximetry); with symptoms indicating central nervous system complications (altered mental status, unconsciousness, drowsiness or difficulty waking up and periodic or constant convulsions (seizures), confusion, severe weakness or paralysis);

2) upon confirmation of a secondary bacterial infection based on laboratory test results or clinical signs (e.g., persistence of a constant high body temperature and other symptoms for more than 3 days);

3) upon the onset of severe dehydration manifested by decreased activity, dizziness, decreased urine output, and lethargy.

Conditions for the provision of medical services

Medical care is provided in the following forms:

• emergency medical care;

• emergency medical care.

Medical care is provided in the form of:

• primary health care;

• emergency medical care, including specialized emergency medical care;

• specialized medical care, including high-tech medical care.

Medical care for adult patients with ARVI can be provided under the following conditions:

• outpatient (in settings not providing round-the-clock medical observation and treatment);

• inpatient (in settings providing round-the-clock medical observation and treatment).

Primary health care is provided to patients on an outpatient basis and in a day hospital setting.

Primary paramedic-led health-care in outpatient settings is provided at feldsher-midwifery stations.

Primary physician-delivered health care is provided by a district general practitioner or general practitioner (family doctor) on an outpatient basis.

Primary specialized health care is provided by an infectious disease specialist of a medical organization providing outpatient care to patients.

Specialized, including high-tech, medical care is provided in an inpatient setting by infectious disease specialists and other specialist physicians and includes the prevention, diagnosis, treatment of diseases and conditions requiring the use of special methods and complex medical technologies, as well as medical rehabilitation.

Patient treatment is carried out in a hospital setting upon referral by a district general practitioner, general practitioner (family doctor), infectious disease specialist, or medical personnel who detected ARVI.

_____________________________________________________________________________

³ _{Resolution of the Chief State Sanitary Doctor of the Russian Federation No. 4 dated January 28, 2021, "On Approval of Sanitary Rules and Norms SanPiN 3.3686-21 'Sanitary and Epidemiological Requirements for the Prevention of Infectious Diseases'."}

⁴ _{Letter of the Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing of the Russian Federation No. 01/17863-9-32 dated November 26, 2009, "On Sending the WHO Document 'Clinical Management of Patients Infected with Pandemic Influenza A (H1N1) 2009 Virus'."}

7. Additional Information

Risk groups for severe ARVI include the following individuals^1,5

• pregnant women at any gestational age and in the postpartum period;

• individuals with chronic lung diseases (bronchial asthma, COPD, etc.);

• individuals with chronic cardiovascular diseases (heart defects, hypertension, coronary artery disease with signs of heart failure, etc.);

• individuals with metabolic disorders (diabetes mellitus, grade 2–3 obesity, etc.);

• individuals with chronic kidney disease;

• individuals with chronic liver diseases;

• individuals with certain neurological conditions (including neuromuscular, neurocognitive disorders, epilepsy);

• individuals with hemoglobinopathies;

• individuals with primary and secondary immunodeficiencies (HIV infection, use of immunosuppressive medications, etc.);

• individuals with malignant neoplasms;

• individuals aged 65 years and older.

¹ _{Resolution of the Chief State Sanitary Doctor of the Russian Federation No. 4 dated January 28, 2021, "On Approval of Sanitary Rules and Norms SanPiN 3.3686-21 'Sanitary and Epidemiological Requirements for the Prevention of Infectious Diseases'."}

⁵ _{Letter of the Russian Ministry of Health No. 30-4/I/1-20714 dated December 2, 2022, "On Sending Guidelines for Medical Workers on the Differential Diagnosis of COVID-19 with Influenza and ARVI, Determination of Management Tactics for Patients, Including Children, Elderly, and Pregnant Women, as well as Guidelines for the Population on the Prevention and Treatment of Seasonal Influenza, COVID-19, RSV Infection, and Other ARVIs."}

Criteria for Evaluating the Quality of Medical Care

References

Appendix A1. Working Group Composition

1. Gorelov A.V. - Academician of the Russian Academy of Sciences, Professor, Deputy Director for Research, Central Research Institute of Epidemiology of Rospotrebnadzor, Head of the Department of Infectious Diseases and Epidemiology, A.I. Evdokimov Moscow State University of Medicine and Dentistry of the Russian Ministry of Health.

2. Malyavin A.G. - Doctor of Medical Sciences, Professor, Professor at the Department of Phthisiology and Pulmonology, Faculty of General Medicine, A.I. Evdokimov Moscow State University of Medicine and Dentistry of the Russian Ministry of Health, Head of the Center for Respiratory Medicine.

3. Chulanov V.P. - Doctor of Medical Sciences, Professor, Deputy Director for Research and Innovative Development, National Medical Research Center of Phthisiopulmonology and Infectious Diseases of the Ministry of Health of the Russian Federation.

4. Zhdanov K.V. - Corresponding Member of the Russian Academy of Sciences, Professor, Doctor of Medical Sciences, Head of the Department and Clinic of Infectious Diseases (with the course of medical parasitology and tropical diseases), S.M. Kirov Military Medical Academy of the Ministry of Defense of the Russian Federation.

5. Lioznov D.A. - Doctor of Medical Sciences, Professor, Director of Smorodintsev Research Institute of Influenza of the Russian Ministry of Health.

6. Esaulenko E.V. - Doctor of Medical Sciences, Professor, Head of the Department of Infectious Diseases in Adults and Epidemiology, Saint Petersburg State Pediatric Medical University of the Russian Ministry of Health.

7. Novak, K.E. - Candidate of Medical Sciences, Associate Professor, Department of Infectious Diseases in Adults and Epidemiology at the Saint Petersburg State Pediatric Medical University of the Russian Ministry of Health.

8. Kravchenko I.E. - Doctor of Medical Sciences, Associate Professor, Professor at the Department of Infectious Diseases, Kazan State Medical University of the Russian Ministry of Health.

9. Pshenichnaya N.Yu. - Doctor of Medical Sciences, Professor, Deputy Director for Clinical and Analytical Work, Central Research Institute of Epidemiology of Rospotrebnadzor.

10. Valishin D.A. - Doctor of Medical Sciences, Professor, Head of the Department of Infectious Diseases with the Course of the Institute of Additional Professional Education, Bashkir State Medical University of the Russian Ministry of Health.

11. Nikiforov V.V. - Doctor of Medical Sciences, Professor, Head of the Department of Infectious Diseases and Epidemiology, Pirogov Russian National Research Medical University of the Russian Ministry of Health.

12. Usenko D.V. - D.Sc. in Medicine, Head of the Educational Center, Leading Researcher, Clinical Department of Infectious Pathology, Central Research Institute of Epidemiology of Rospotrebnadzor.

13. Maltsev O.V. - Ph.D. in Medicine, Deputy Head of the Department and Clinic of Infectious Diseases (with a course in medical parasitology and tropical diseases), Kirov Military Medical Academy of the Ministry of Defense of the Russian Federation.

14. Pozdnyakova M.G. - Ph.D. in Medicine, Senior Researcher, Laboratory for Testing New Protective Agents Against Viral Infections, Smorodintsev Research Institute of Influenza of the Russian Ministry of Health.

All working group members are members of the Pokrovsky National Association of Infectious Disease Specialists (NAIS) or the Russian Scientific Medical Society of Therapists (RSMST).

There is no conflict of interest.

Appendix A2. Methodology for Developing Clinical Guidelines

Target audience of the clinical guidelines:

1. Infectious disease specialist;

2. General practitioner (internist);

3. General practitioner (family physician);

4. Medical students, residents, postgraduate students.

In these clinical guidelines, all data are ranked by level of reliability (evidence) depending on the quantity and quality of studies on the issue.

Table A1 – Scale for assessing Levels of Evidence (LoE) for diagnostic methods (diagnostic interventions)

⁶ _{The generally accepted standard for clinical trials of diagnostic interventions is a cross-sectional study design in which the diagnostic method under study and the reference method (the "gold standard" for diagnosing the disease or condition under study) are applied in parallel and under identical conditions to each included patient. The study and reference methods must be applied independently of each other (i.e., the study method cannot be part of the reference method) and must be interpreted by the investigator without knowledge of the results of the other method (blinding is recommended).}

Table A2 – Scale for determining Grades of Recommendation (GoR) for diagnostic interventions

Table A3. Possible combinations of LoE and GoR for diagnostic interventions

*_{If a single clinical trial is evaluated, this condition is not taken into account}

Table A4 – Scale for assessing Levels of Evidence for prevention, treatment, and rehabilitation methods (preventive, therapeutic, and rehabilitative interventions)

Table A5 – Scale for assessing Grades of Recommendation (GoR) for methods of prevention, diagnostics, treatment, and rehabilitation (preventive, diagnostic, therapeutic, and rehabilitative interventions)

Procedure for updating clinical guidelines

The mechanism for updating clinical guidelines provides for their systematic revision at least once every three years, as well as upon the emergence of new evidence-based medicine data on the diagnosis, treatment, prevention, and rehabilitation of specific diseases, or in the presence of justified additions/comments to previously approved clinical guidelines, but no more frequently than once every 6 months.

Appendix A3. Reference Materials

These clinical guidelines were developed taking into account the following regulatory documents:

1. Federal Law No. 157-FZ of September 17, 1998, "On Immunoprophylaxis of Infectious Diseases."

2. Federal Law of the Russian Federation No. 326-FZ of November 29, 2010, "On Compulsory Medical Insurance in the Russian Federation."

3. Federal Law No. 323-FZ of November 21, 2011, "The Fundamentals of Healthcare Protection of Citizens in the Russian Federation."

4. Order of the Ministry of Health and Social Development of Russia No. 494 dated August 9, 2005, "On the Procedure for the Use of Medicinal Products in Patients for Vital Indications".

5. Order of the Ministry of Health of the Russian Federation No. 804n dated October 13, 2017, "On Approval of the Nomenclature of Medical Services."

6. Order of the Ministry of Health and Social Development of Russia No. 69n of January 31, 2012, "On Approval of the Procedure for Providing Medical Care to Adult Patients with Infectious Diseases."

7. Order of the Russian Ministry of Health No. 205n of May 2, 2023, "On Approval of the Nomenclature of Positions of Medical and Pharmaceutical Workers."

8. Order of the Russian Ministry of Health No. 700n of October 7, 2015, "On the Nomenclature of Specialties of Specialists with Higher Medical and Pharmaceutical Education."

9. Order of the Ministry of Labor of Russia No. 374n of July 26, 2024, "On the Classification and Criteria Used in Carrying Out Medical and Social Expertise of Citizens by Federal State Institutions of Medical and Social Expertise."

10. Order of the Russian Ministry of Health No. 203n dated May 10, 2017, "On Approval of the Criteria for Assessing the Quality of Medical Care".

11. Order of the Chief State Sanitary Doctor of the Russian Federation No. 4 dated January 28, 2021, "On Approval of Sanitary Rules and Norms SanPiN 3.3686-21 'Sanitary and Epidemiological Requirements for the Prevention of Infectious Diseases'."

12. Letter of the Russian Ministry of Health No. 30-4/I/1-20714 dated December 2, 2022, "On Sending Guidelines for Medical Workers on Conducting Differential Diagnosis of COVID-19 with Influenza and ARVI, Determining Management Tactics for Patients, Including Children, Elderly Individuals, and Pregnant Women, as Well as Guidelines for the Public on the Prevention and Treatment of Seasonal Influenza, COVID-19, RSV Infection, and Other ARVI."

13. Order of the Ministry of Health of the Russian Federation No. 330 dated August 5, 2003, "On measures to improve therapeutic nutrition in healthcare institutions of the Russian Federation".

14. Order of the Ministry of Health of the Russian Federation No. 395n dated June 21, 2013, "On approval of therapeutic nutrition standards".

15. Order of the Ministry of Health of the Russian Federation No. 1008n dated September 23, 2020, "On approval of the procedure for providing patients with therapeutic nutrition".

Appendix A3.1 Clinical characteristics of main respiratory tract lesion syndromes

Appendix A3.2 ARVI pathogens and main respiratory tract lesion syndromes

Appendix A3.3 ARVI severity criteria

Appendix A3.4 Differential diagnosis of influenza and other ARVIs

* _{SARS – severe acute respiratory syndrome}

** _{RSV infection – infection caused by respiratory syncytial virus}

Appendix A3.5 Medical services during outpatient monitoring for treatment of the disease (if necessary), condition assessment, and treatment monitoring

Appendix B. Physician Action Algorithms

Appendix C. Patient Information

In clinical practice, there is a collective concept of "acute respiratory viral infections" (ARVI), which includes a number of predominantly upper respiratory tract diseases caused by viruses, including parainfluenza viruses, respiratory syncytial virus, adenoviruses, rhinoviruses, human coronaviruses, including the coronavirus causing severe acute respiratory syndrome (SARS).

They are capable of causing clinical manifestations of the disease familiar to humans, such as acute rhinitis (runny nose), pharyngitis (inflammation of the oropharyngeal mucosa accompanied by sore throat and mucosal redness), laryngitis (inflammation of the laryngeal mucosa where the vocal cords are located, accompanied by hoarseness or loss of voice), and involvement of the lower respiratory tract—the trachea (tracheitis) and bronchi of various calibers (bronchitis). When the larynx and lower respiratory tract are affected, a common symptom is a cough, which is initially dry, without sputum production, and then becomes wet, with sputum.

With ARVI, a person also often experiences weakness, malaise, fever, and sometimes headaches. This is due to intoxication against the background of viral particle breakdown, as well as the destruction of certain body cells and the release of toxic substances into the blood.

Despite the fact that the group of diseases known as ARVI is well known and familiar to almost everyone, and they are usually transient and end favorably, one must know that they should not be treated as something simple and non-serious. These are infectious diseases that can be mild, moderate, or sometimes severe, manifested by high fever (pyrexia), and in rare cases, the development of complications such as inflammation of the brain membranes (meningitis) and brain edema, as well as respiratory and cardiovascular failure, which can lead to a fatal outcome.

These complications are more common in elderly people with comorbid conditions. Children, whose immune systems are immature, are also susceptible to complications.

Additionally, ARVI can be complicated by the addition of secondary bacterial flora, such as otitis media (inflammation of the ear manifested by constant or pulsating, shooting ear pain), sinusitis (maxillary sinusitis, frontal sinusitis), bronchitis, and pneumonia. Bronchitis can be a manifestation of the disease (in certain viral infections) or a bacterial complication of ARVI. In the latter case, the sputum acquires a greenish, purulent character. ARVI is frequently complicated by bronchitis in smokers.

ARVI are socially and economically significant diseases. The reason for this is the high incidence rate in the human population compared to other diseases.

How to protect yourself from ARVI.

A number of non-specific measures can be used for the prevention of ARVI:

1. Avoid hypothermia. It is especially important to keep your feet warm and avoid breathing air through an open mouth in cold weather. Do not stay outside in severe frost for more than 20 minutes. Do not go outside in the cold while intoxicated or drink hot beverages before going out—this contributes to hypothermia. Also, do not go outside while heavily sweating. Avoid prolonged exposure to direct airflow near air conditioners and in drafts.

2. Avoid close contact with individuals having ARVI. Do not share eating utensils.

3. Wearing a mask in public places. However, a mask is effective only until it becomes damp (from sweat, etc.).

4. Rinsing the nasopharynx and oropharynx with water after visiting public places.

5. Chemoprophylaxis.

If symptoms of ARVI appear, it is recommended to seek medical care at a polyclinic or call a doctor to your home (if the temperature exceeds 38.5^°C). Do not self-medicate!

It is especially important to seek medical care in case of high body temperature, dyspnea, persistent headache, repeated vomiting that brings no relief, or a pronounced drop in blood pressure!

Appendix G. Assessment Scales, Questionnaires, and Other Evaluation Tools

Not applicable.