Viral Pneumonia: Clinical Guidelines

List of Abbreviations

BP – blood pressure

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

Chest CT – computed tomography of the chest organs

Chest X-ray – radiography of the chest organs

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

ARF – acute respiratory failure

ARDS – acute respiratory distress syndrome

CHI – Compulsory Health Insurance

ARVI – Acute respiratory viral infections

ICU – intensive care unit

RF – Russian Federation

FL – Federal Law

RR – respiratory rate

HR – heart rate

SARS-CoV-2 – novel coronavirus infection causing the COVID-19 pandemic

Terms and Definitions

Evidence-based medicine is an approach to medical practice that aims to optimize decision-making by emphasizing the use of evidence from well-designed and well-conducted research regarding the effectiveness and safety of prophylactic, diagnostic, and therapeutic interventions, while such evidence is searched, compared, summarized, and widely disseminated for patient care

Disease – a disorder of bodily function, working capacity, and the ability to adapt to changing environmental and internal 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 through 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 impairment of their functions caused by the disease or condition or their complication;

Outcomes of diseases – medical and biological consequences of a disease;

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

Complication of a disease – addition of a physiological process impairment syndrome to the disease; - violation of the integrity of an organ or its wall; - hemorrhage; - developed acute or chronic failure of an organ function or an organ system;

Instrumental diagnostics – diagnostics using various devices, apparatuses, and instruments to examine a patient.

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 test material using various specialized equipment.

Patient model – a set of clinical, laboratory, and instrumental diagnostic features allowing to identify a disease (poisoning, trauma, physiological state) and classify it into a group of conditions with common etiology and pathogenesis, clinical manifestations, and general approaches to treatment and condition correction;

Medical worker– an individual who has 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 is 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, pathogenesis, and clinical manifestations.

Syndrome – a condition developing as a consequence of a disease and defined by a set of clinical, laboratory, and instrumental diagnostic signs that allow its identification and classification into a group of conditions with varying etiologies but common pathogenesis, clinical manifestations, and general treatment approaches, which nevertheless depend on the diseases underlying the syndrome.

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

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

1. Brief information on the disease or condition

1.1 Definition of the disease or condition

Viral pneumonia (VP) – acute inflammation of the respiratory divisions of the lungs caused by viral pathogens, presenting with intoxication and respiratory failure syndromes [1-7].

After identifying the viral pathogen, it is necessary to consider the possibility of bacterial coinfection and determine whether antibacterial therapy is needed [94].

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

Currently, it is recognized that the prevalence of viral infection in patients with pneumonia reaches 27% [95].

Viral pneumonia can be caused by a large number of viruses containing RNA or DNA as their nucleic acid [96].

Respiratory syncytial virus (RSV)

• RNA virus

• RSV is the most common cause of viral pneumonia in young children and infants.

Rhinovirus

• RNA

• Rhinovirus is the most common cause of upper respiratory tract infection across all age groups, although it is less frequently encountered as a cause of viral pneumonia.

Influenza viruses A, B, and C

• RNA

• Influenza A is the leading cause of mortality and morbidity among viral types of pneumonia.

• There are several subtypes of influenza A. Two subtypes of particular concern – are avian influenza (H5N1) and swine influenza (H1N1).

Human metapneumovirus

• RNA

• Human metapneumovirus – is an emerging viral pathogen increasingly recognized as a cause of viral pneumonia and considered responsible for atypical pneumonia outbreaks.

Parainfluenza viruses types 1, 2, 3, and 4

• RNA

• Parainfluenza virus has several serotypes and is most commonly associated with pneumonia-like illness in young children on a seasonal basis. Spring and autumn predominate.

Human bocavirus Coronavirus

• RNA

• Coronaviruses – are viruses causing pneumonia, typically in immunocompromised individuals.

• However, one coronavirus subtype causes Middle East respiratory syndrome, and another – severe acute respiratory syndrome.

Adenovirus

• DNA

• Adenovirus most commonly causes pneumonia in solid organ transplant or hematopoietic stem cell transplant recipients.

Enteroviruses

• RNA

• Enteroviruses, although common causes of poliomyelitis, gastrointestinal, and upper respiratory syndromes, less frequently cause viral pneumonia.

Varicella-zoster virus

• DNA

• Varicella-zoster virus is associated with both chickenpox and shingles and can cause severe forms of pneumonia, particularly in unimmunized pregnant women and non-pregnant adults with chickenpox. It is a fairly common cause of pneumonia in individuals with HIV following a shingles outbreak.

Hantavirus

• RNA

• Hantavirus – a zoonotic viral pathogen originating in the American Southwest and associated with rodent excreta exposure.

• Hantavirus pneumonia is frequently associated with rapid respiratory failure and cardiovascular failure.

Epstein-Barr virus (EBV)

• DNA

• Epstein-Barr virus, although frequently involved in mononucleosis-like syndromes, is rarely associated with viral pneumonia. Most cases occur in individuals with hematological disorders.

Human herpesviruses 6 and 7

• DNA

Herpes simplex virus

• DNA

• HSV I and II are associated with viral pneumonia in immunocompromised patients, including those with HIV, as well as solid organ and hematopoietic transplant recipients.

Cytomegalovirus (CMV)

• DNA

• Cytomegalovirus is a significant cause of pneumonia in HIV-infected patients with a CD4 count below 100 cells per cubic millimeter.

• Cytomegalovirus is also a frequent cause of pneumonia in solid organ and hematopoietic transplant recipients.

Measles

• RNA

• A childhood exanthematous disease which, although less common in the industrialized world due to vaccination, remains a major contributor to childhood mortality worldwide as a result of viral pneumonia complications.

Middle East respiratory syndrome (coronavirus)

• RNA

• A coronavirus subspecies associated with severe pneumonia. First identified in the Middle East with an initial mortality rate of 30%.

Severe acute respiratory syndrome (metapneumovirus)

• RNA

• A coronavirus subspecies causing life-threatening pneumonia

A meta-analysis by Burk M et al. demonstrated that influenza and rhinovirus were the most frequently detected viruses. Respiratory syncytial virus, coronavirus, parainfluenza, adenovirus, and human metapneumovirus play a smaller but notable role in community-acquired pneumonia (CAP), being detected in 1–4% of patients. Viruses detected in <1% of the CAP population include enterovirus, varicella-zoster virus, and herpes simplex virus [97].

Infection with SARS-CoV-2 certainly plays a role in the development of CAP, but it must be emphasized that in the current season, severe cases of disease accompanied by lung involvement are extremely rare. COVID-19 typically presents mildly, akin to a seasonal respiratory infection. From a clinical perspective, it is worth bearing in mind that there are no pathognomonic signs of COVID-19, just as with other viral diseases, and the diagnosis is established solely on the basis of laboratory diagnostics (rapid immunochromatographic assay, polymerase chain reaction) [98].

All of the aforementioned viruses are causative agents of community-acquired pneumonia regardless of the patient's age. The incidence of respiratory viruses in patients with community-acquired pneumonia is highly seasonal, increasing during the autumn-winter period. A distinction is made between primary viral pneumonia (resulting from the direct cytopathic effect of the virus on lung tissue) and secondary bacterial pneumonia, which may coincide with the primary pulmonary lesion or be a late complication of viral respiratory infection (primarily influenza).

In adults, viruses are the suspected causative agents in one-third of community-acquired pneumonia cases, particularly influenza viruses, rhinoviruses, and coronaviruses, though the relative frequency of different infections may vary significantly over time and across regions. Furthermore, when evaluating the dynamic etiology of viral pneumonia, the variability of diagnostic tests used must be taken into account. Despite being caused by various pathogens, CAP is characterized by common transmission pathways, many stages and pathogenetic features, as well as clinical manifestations [1-7]. The virus almost invariably enters the respiratory tract via airborne droplets. When entering as relatively large droplets, the primary localization of the viral process is the respiratory mucosa, and the development of pneumonia may be associated with the "descending" spread of infection. Alternatively, the virus enters within micro-droplets (generated during forceful sneezing and coughing) and immediately reaches the distal respiratory divisions, which is characteristic of epidemic influenza with a typical hyperacute onset.

To initiate the infectious process, viruses must begin replication in susceptible cells, which can lead to the formation of both complete and defective viral particles. Four possible outcomes of virus-cell interaction are known: cytopathic effect, cytoproliferative effect, formation of viral inclusion bodies, and viral persistence within the cell. The cytopathic effect is best studied in epidemic influenza—active viral replication in various epithelial cells and macrophages leads to characteristic cellular alterations (appearance of "grippe cells") followed by cell death via cytolysis. The cytoproliferative effect is most characteristic of paramyxoviruses, but may also be associated with other pathogens. The intracellular pathogen stimulates either the formation of characteristic cellular proliferations or the appearance of bi- and multinucleated cells. Virus-containing basophilic intranuclear inclusion bodies are characteristic of DNA viral infections (adenovirus and herpes simplex), followed by cell death via apoptosis.

A significant role in the pathogenesis of viral respiratory infections and their accompanying symptoms is played by changes associated with hemodynamic disturbances and other "nonspecific" (i.e., not directly virus-induced) alterations: congestion, petechial hemorrhages, microthrombosis, serous edema, occasionally hyaline membrane formation, and dyselectasis. The severity of these changes correlates with the clinical presentation (both intoxication signs and respiratory failure). The mechanisms of their development are mediated by cytokines, primarily produced by macrophages and associated with endothelial damage. Endothelial lining damage plays a significant role. When such changes reach maximal severity, it is customary to refer to diffuse alveolar damage (adult respiratory distress syndrome, shock lung).

With a prolonged course of the inflammatory process, lymphoid cells appear within the alveolar septa, which, combined with moderate fibrosis, warrants the diagnosis of true interstitial pneumonia [5,6].

1.3 Epidemiology of the Disease or Condition

Viral pneumonias are among the most common diseases, occurring at any age and having specific clinical features across various age groups. Viruses enter the human body via airborne droplet or contact transmission [1-4,7].

Annually, about 200 million cases of viral community-acquired pneumonia are registered worldwide: 100 million in children and 100 million in adults. Both men and women are equally affected. In immunocompromised individuals, it develops regardless of age. Viral pneumonia frequently occurs in children under three years of age (even with a good immune system), particularly against the background of infections caused by respiratory syncytial virus. In adults without immune dysfunction, CAP most commonly has a mild course [1-4,7].

In 2020, the incidence of community-acquired pneumonia increased more than 3.5-fold compared to the previous year, with a rate of 1,856.2 per 100,000 population against a long-term average incidence of 397.4 (2011–2020). Meanwhile, the incidence of viral pneumonia increased more than 100-fold relative to the previous year, reaching 783.08 per 100,000 population compared to 7.2 per 100,000 population in 2019. In 2021, the incidence of community-acquired pneumonia (rate of 1,148.43 per 100,000 population) increased 2.9-fold compared to the long-term average (LTA of 391.82) (in 2020 – 1,856.18). The incidence of viral pneumonia (265.06 per 100,000 population) increased 45.1-fold relative to the LTA (5.88) (in 2020 – 783.08). This situation is explained by the fact that in 2020, cases of community-acquired pneumonia caused by the novel coronavirus infection were recorded in the federal statistical observation form No. 2 "Information on Infectious and Parasitic Diseases" together with community-acquired viral pneumonia. Starting in 2021, cases of pneumonia caused by the novel coronavirus have been registered separately, which prevents a reliable assessment of the difference in incidence rates over the past two years. In 2022, the total number of registered community-acquired pneumonia cases decreased to pre-COVID levels (2022 rate – 407.29 per 100,000 population). In 2023, the incidence of community-acquired pneumonia (the rate was 498.02 per 100,000 population) increased both compared to the previous year and relative to the LTA. The incidence growth rate relative to the previous year was 22%, and the long-term average incidence was exceeded by 25% (LTA – 398.41 per 100,000 population). Until 2020, bacterial pneumonia predominated in the structure of verified community-acquired pneumonia, but with the onset of the novel coronavirus pandemic, the situation changed. The incidence of viral pneumonia (62.40 per 100,000 population) relative to the LTA (5.88) increased 10.6-fold in 2022 and decreased 4.2-fold relative to the previous year (in 2021 – 265.06). The number of coronavirus-induced pneumonia cases also decreased significantly due to the predominance of the Omicron variant, which mainly affects the upper respiratory tract. In the structure of laboratory-confirmed cases of community-acquired pneumonia in 2022, the proportion of viral pneumonia accounted for 15.32% of the total number, and bacterial pneumonia for 12.30%. In 2023, a significant 2.3-fold decrease in the incidence of viral pneumonia was noted (the rate was 62.4 per 100,000 population in 2022 and 26.98 per 100,000 population in 2023) [8].

The highest number of deaths from community-acquired pneumonia in adults and children in the Russian Federation was recorded in 2020, which is explained by the dominance during this period of the circulating Delta coronavirus, which predominantly affects the lower respiratory tract [8].

In most cases, CAP is characterized by a mild course; however, in elderly and senile individuals, or in the presence of concomitant bronchopulmonary, cardiovascular diseases, or immunodeficiency, it can be associated with the development of severe, life-threatening complications. In 10-30% of patients with pneumonia, mixed or co-infection occurs, which may be caused by a combination of various bacterial pathogens (S. pneumoniae with H. influenzae or M. pneumoniae), or their combination with respiratory viruses. Viral pneumonias caused by pathogen associations are characterized by a more severe course and an unfavorable prognosis [1-7].

1.4 Features of Coding the Disease or Condition

I. International Classification of Diseases, 10th Revision (ICD-10):

J12: Viral pneumonia, not elsewhere classified

J12.0 Adenoviral pneumonia

J12.1 Respiratory syncytial virus pneumonia

J12.2 Parainfluenza virus pneumonia

J12.3 Pneumonia due to human metapneumovirus

J12.8 Other viral pneumonia

J12.9 Viral pneumonia, unspecified

1.5 Classification of the disease or condition

[1-7].

I. Etiological classification of viral pneumonia indicating the pathogen):

Common causes of viral pneumonia:

• influenza viruses type A, B;

• respiratory syncytial virus;

• adenovirus;

• parainfluenza virus;

Sometimes caused by:

• SARS-CoV virus – causes severe acute respiratory syndrome;

• MERS-CoV coronavirus – causes Middle East respiratory syndrome;

• SARS-CoV-2 coronavirus – causes the novel coronavirus infection COVID-19.

Rare causes include:

• varicella-zoster virus, rubella virus, herpes simplex virus – in newborns;

• cytomegalovirus infection – in immunocompromised individuals;

• hantavirus.

II. According to clinical and morphological characteristics:

• parenchymal (alveolar): lobar, focal (bacterial)

• interstitial (viral)

• mixed (viral-bacterial)

III. Classification of pneumonia by setting of acquisition:

• community-acquired pneumonia – develops outside the hospital or within the first two days after hospitalization;

• nosocomial (hospital-acquired) pneumonia – develops two days or more after hospitalization.

IV. Classification of pneumonia by localization and extent:

• subsegmental: affects less than one pulmonary segment;

• segmental: affects one or several segments;

• lobar: affects a pulmonary lobe;

• unilateral: affects one lung (left-sided, right-sided);

• bilateral: affects both lungs;

• total.

V. Classification of pneumonia by severity (description of severity grades in Appendix A3)

• non-severe

• severe

VI. Disease course:

• acute (up to 3–4 weeks)

• protracted (more than 3–4 weeks)

VII. Complications associated with the course of viral pneumonia:

• acute respiratory failure;

• acute respiratory distress syndrome;

• secondary (bacterial) pneumonia.

VIII. Complications associated with the development of secondary (bacterial) pneumonia:

• acute respiratory failure;

• acute respiratory distress syndrome

• septic shock;

• sepsis

• pleurisy and pleural empyema (purulent pleurisy);

• lung abscess;

• meningitis;

• myocardial dystrophy and myocarditis, etc.

Below is an example of a clinical diagnosis formulation:

Primary disease: influenza A H1N1, severe course, viral lung injury.

Complications: ARF.

Primary disease: novel coronavirus infection COVID-19 (confirmed), severe course. Bilateral viral lung injury (CT-3, 60%). U07.1

Complications: ARDS, ARF. Nosocomial destructive pneumonia caused by Klebsiella pneumoniae.

1.6 Clinical presentation of the disease or condition

In most cases the development of viral pneumonia is preceded by ARVI symptoms. The disease typically begins acutely with the onset of toxindromic manifestations (fever up to subfebrile or febrile levels, generalized weakness, headache, myalgia, and arthralgia), as well as catarrhal (catarrhal-respiratory) syndrome—development of cough, rhinorrhea, and in some cases conjunctivitis [11].

With the progression of viral lung injury and at the peak of the infection's clinical manifestations, the main symptom is progressive dyspnea exceeding 30 respiratory movements per minute (acute respiratory failure). Clinical symptoms: diffuse cyanosis, tachycardia, patient agitation rapidly replaced by apathy, possible loss of consciousness, and a drop in systolic blood pressure below 90 mm Hg. Cough with scant bloody sputum (sputum shows mononuclearocytosis).

In a retrospective analysis, T. Ishiguro demonstrated that symptoms such as sore throat, fever, dyspnea, and dry cough were more common in patients with a confirmed diagnosis of viral pneumonia than in patients with other conditions [61].

The development of secondary (bacterial) pneumonia should be suspected:

1. When fever persists (body temperature above 37.5°C) for more than 3–4 days despite adequate antiviral therapy.

2. When a second wave of fever appears in combination with a productive cough and chest pain.

3. When coughing is combined with chest pain, or chest pain associated with breathing in the absence of a cough.

4. When shortness of breath occurs during normal physical exertion.

5. In case of localized dullness of percussion note and/or localized moist rales (foci of crepitation).

2. Diagnostics, medical indications and contraindications for diagnostic methods

Distinctive features of viral pneumonia:

1. At the onset – a typical picture of acute respiratory viral infection (ARVI), minimal auscultatory changes, minimal changes on chest radiography.

2. "Rapid" progression of the disease course.

3. Development of acute respiratory distress syndrome (ARDS).

4. Absence of leukocytosis and significant elevation of CRP.

Diagnostic criteria

To verify the viral genesis of pneumonia, it is necessary^[1]:

1) clarify the epidemiological history (whether the patient had contact with an ARVI patient in their environment or family, whether the patient or their contacts and relatives were abroad in the preceding 14 days,

2) test sputum (or, in its absence, a combined respiratory swab) using PCR for influenza and coronavirus infection to confirm and identify the viral etiology of the disease (upon hospitalization: mandatory for everyone on the day of admission or the following morning after hospitalization).

3) All patients, during home visits, emergency room examinations, etc., must have their saturation measured with a pulse oximeter; hospitalization is recommended if influenza is suspected.

4) For all patients examined at home or admitted to the emergency department of a medical organization (including in an infectious diseases department) – perform chest radiography (anteroposterior + lateral view), pulse oximetry (with recording of results in the patient's medical record!) and prescribe a complete blood count with leukocyte differential (viral pneumonia is characterized by leukopenia, thrombocytopenia, and lymphopenia). There are no pathognomonic anamnestic features or physical examination findings for diagnosing viral pneumonia as opposed to bacterial pneumonia. Clinical, radiological, and laboratory data commonly used for differential diagnosis are presented in Appendix A3.

^[1] Letter of the Russian Ministry of Health dated 06.03.2020 N 30-4/I/2-2702 "On the distribution of the algorithm for providing medical care to the adult population with community-acquired pneumonia"

2.1 Complaints and Anamnesis

^[1] SanPiN 3.3686-21 "Sanitary and epidemiological requirements for the prevention of infectious diseases. XXXIV. Prevention of influenza and other acute respiratory viral infections (Decree of the Chief State Sanitary Doctor of the Russian Federation No. 2 dated 28.01.2021)].

2.2 Physical Examination

Comments: pulse oximetry is a simple and reliable screening method that allows for the detection of patients with hypoxemia in need of respiratory support and the assessment of its efficacy

− chest palpation with determination of vocal fremitus;

− comparative percussion of the lungs − to detect possible changes in the percussion note (symptom of pulmonary tissue consolidation);

− lung auscultation − to detect pathological respiratory sounds (dry and moist rales, crepitation, and their prevalence), bronchophony, and assessment of inspiration and expiration phases.

Comments:

1. Vocal fremitus and bronchophony (increased resonance of voice sounds heard during auscultation) − enhanced over the affected lung area.

2. Percussion note − shortening (dullness) of the percussion note over the affected lung area; asymmetry of the percussion sound when comparing symmetrical areas of both lungs indicates consolidation and/or pleural effusion.

3. Breathing − locally audible bronchial breathing with weakened inspiration, and prolonged, enhanced expiration.

4. Rales − locally determined resonant fine moist rales and/or crepitation, "pleural friction rub" phenomenon.

These signs, detected during direct examination of the patient, indicate changes in the area of pneumonic infiltration (alveolar exudation, focus of bacterial pneumonia)

GoR CLoE 5Grade of Recommendation C (Level of Evidence – 5).

2.3 Laboratory Diagnostics

2.3.1. Nonspecific laboratory diagnostics

Comments: uncomplicated viral infection is typically characterized by normocytosis or leukopenia, neutropenia, eosinopenia, relative lymphocytosis, and monocytosis. In bacterial complications (pneumonia, sinusitis, etc.), blood tests show increasing leukocytosis, stab neutrophilia, and elevated erythrocyte sedimentation rate (ESR). Interstitial viral lung involvement is characterized by leukopenia, neutrophilia with a stab shift, anemia, and thrombocytopenia.

Comments: CRP levels correlate with disease severity, extent of inflammatory infiltration, and prognosis in CAP. At a CRP concentration >100 mg/L, its specificity in confirming a diagnosis of bacterial pneumonia exceeds 90%. Conversely, at a CRP concentration <20 mg/L, the diagnosis of bacterial pneumonia is unlikely.

Comments: in an uncomplicated viral infection, there are no pathological changes; in cases of pronounced fever or intoxication syndrome, an increase in urine specific gravity, mild transient leukocyturia, proteinuria, and cylindruria may occur, which disappear upon normalization of body temperature and relief of general infectious intoxication symptoms.

Comments: detected abnormalities may indicate organ dysfunction, decompensation of concomitant diseases, and the development of complications, which influences the choice of medications and their dosing regimen [64]. An increase in LDH, CK, and myoglobin concentrations may indicate viral lung damage in the context of severe influenza. The determination of these parameters can be used both for additional diagnostic purposes (an increase in myoglobin concentration [infectious rhabdomyolysis] is accompanied by the development of acute kidney injury) and to decide on the use of extracorporeal detoxification methods [65,66].

Comments: an increase in D-dimer 3–4 times above the age-adjusted normal limit, prolongation of prothrombin time, especially in severe cases (decrease in prothrombin %), and an elevation of fibrinogen are of clinical significance.

Comment: as a "decision-making threshold" indicating a bacterial infection, it is recommended to use a PCT level of 0.5 ng/mL and higher. In severe cases of the disease, determining PCT alongside CRP is mandatory. The PCT level correlates with the severity of pneumonia [67] and can serve as an additional criterion (alongside CRP) for differential diagnosis between viral lung injury and secondary (bacterial) pneumonia. In lung injury in patients with SARS-CoV-2 or acute interstitial pneumonia — AIP (in systemic connective tissue diseases — rheumatoid arthritis, systemic lupus erythematosus, etc., "methotrexate lung", etc.), high CRP levels and leukocytosis are frequently observed, yet the PCT level remains within normal limits [7,50–52,62,63,66,67,68].

Comments: Measurement of paO2, paCO2, pH, and bicarbonates allows for a more precise determination of the presence and severity of respiratory failure and metabolic disorders, and helps optimize respiratory support. An elevated arterial blood lactate level is a marker of hypoperfusion and an unfavorable prognosis in severe community-acquired pneumonia.

2.3.2. Specific laboratory diagnostics

Laboratory testing to identify the causative agent of influenza and acute respiratory infection is mandatory in the following cases [1]:

- in outpatient settings — for all individuals with symptoms of a influenza-like illness who sought medical care no later than 2 days

- upon hospitalization of a patient for acute respiratory viral infections of the upper and lower respiratory tracts (severe and unusual forms of the disease) (inpatient care settings);

- for individuals at high risk for an unfavorable outcome of influenza and acute respiratory viral infections (pregnant women, persons with chronic heart or lung diseases, metabolic syndrome, immunodeficiencies, individuals over 60 years of age, and others) (outpatient care settings);

- upon registration of outbreaks of acute respiratory viral infections with multiple cases in organized adult communities with 5 or more affected individuals within a single incubation period, or illness in individuals from round-the-clock residential institutions (outpatient care settings)

Comments: use of rapid immunochromatographic assays (ICA) for the presence of influenza A and B virus antigens, respiratory syncytial virus, adenovirus, and SARS-CoV-2 coronavirus (rapid immunochromatographic testing of a nasopharyngeal swab for influenza A virus, influenza B virus, Human Adenovirus, Human Respiratory Syncytial virus, and SARS-CoV-2 coronavirus) in patients who sought medical care no later than 2 days from the onset of symptoms.

GDR CLE 5Grade of recommendation C (level of evidence – 5)

Comments: Molecular biological testing of nasopharyngeal and oropharyngeal swabs for SARS-CoV-2 coronavirus, influenza A and B viruses (Influenza virus A, B), molecular biological testing of swabs from the nasopharynx and oropharynx for parainfluenza viruses (Human Parainfluenza virus), rhinoviruses (Human Rhinovirus), adenovirus (Human Adenovirus), respiratory syncytial virus (Human Respiratory Syncytial virus), coronaviruses 229E, OC43, NL63, HKUI (Human Coronavirus), bocavirus (Human Bocavirus), metapneumovirus (Human Metapneumovirus) — identification 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 progression and complications. When lower respiratory tract disease is suspected, an examination of sputum, tracheal or pharyngeal aspirates, and bronchoalveolar lavage fluid is performed. This is the most effective method, allowing the detection of viral nucleic acids on average up to 7 days, and maximally up to 2 weeks from disease onset (provided upper respiratory tract involvement signs persist). Results are obtained within 4–6 hours after sample submission.

Comments: the criteria for establishing a diagnosis of bacterial community-acquired pneumonia are determined by the presence in the patient of radiologically confirmed focal infiltration of lung tissue and at least two clinical symptoms and signs from the following list [69].

1. acutely onset fever at the beginning of the disease (fever above 38 degrees Celsius, productive cough with or without purulent sputum);

2. physical signs (focus of crepitation / fine moist rales, bronchial breathing, dullness on percussion);

3. leukocytosis >10 × 10⁹ /L, elevated C-reactive protein (CRP) >50 mg/L.

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

^[1] SanPiN 3.3686-21 "Sanitary and epidemiological requirements for the prevention of infectious diseases. XXXIV. Prevention of influenza and other acute respiratory viral infections" (Resolution of the Chief State Sanitary Doctor of the Russian Federation No. 2 dated January 28, 2021)

2.4 Instrumental Diagnostics

Comments: signs most indicative of viral pneumonia include the following: [63,96]

- Interstitial infiltrates – "ground-glass opacities" are observed when inflammatory exudate fills the interalveolar spaces;

- uneven distribution of interstitial infiltrates;

- bilateral widespread infiltrates;

- pneumonia-like syndrome with a normal chest X-ray (they usually lack distinct physical examination symptoms and may not be visible on radiography).

Respiratory viruses (influenza, SARS-CoV-2, etc.) are most frequently associated with diffuse bilateral "ground-glass" lung lesions.

Signs indicative of bacterial pneumonia include the following:

- alveolar infiltrates (the main radiological sign of bacterial CAP is a focal localized decrease in lung airlessness (infiltration) due to the accumulation of inflammatory exudate in the respiratory divisions);

- lobar consolidation (when inflammatory exudate fills the air-containing alveoli, alveolar sacs, alveolar ducts, and respiratory bronchioles within a lung lobe);

- the presence of limited unilateral involvement in the form of a lung tissue consolidation area increases the probability of bacterial pneumonia.

- density of nodules (micronodules);

- pleural effusion.

Comments: Chest CT has higher sensitivity and specificity in diagnosing CAP compared to chest radiography. Chest CT is recommended for patients with a high clinical and laboratory probability of CAP, but with no infiltration on chest radiography, as well as when obtaining images that cannot be unequivocally interpreted as pneumonia-induced infiltration. CT signs of viral pneumonia: frequently encountered bilateral lung involvement with "ground-glass opacities", their localization, consolidation, more often with a bilateral process, thickening of the interlobular septa or "crazy-paving" pattern, "reversed halo" sign, and reticular changes.

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

Comments: the risk of rhythm disorders, acute coronary syndrome, and decompensation of chronic comorbidities increases. Their timely detection and correction affect the patient's prognosis. In addition, a number of ECG changes – QT interval prolongation, early ventricular repolarization syndrome – affect the choice of medicinal products and antibacterial drugs.

GPP CGrade of Recommendation C (Level of Evidence − 5).

2.5 Other Procedures

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

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

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

• preventing the further progression of the pathological process caused by the disease, achieving a complete and stable recovery;

• prevention of potential disease complications;

• consideration of optimal therapeutic (antimicrobial therapy) management for patients presenting with criteria for bacterial infection and/or coinfection [94].

Treatment tactics are influenced by the following factors [1-7]: stage of the disease; severity of the disease; clinical form of the disease; leading clinical manifestations and course features considering signs of immunodeficiency (chronic alcoholism, cachexia, 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 medications contained in these guidelines may differ from the information specified in the summary of product characteristics (SPC). For complete information on the use of a particular medicinal product, consult the SPC. Personal responsibility for the interpretation and use of these guidelines rests with the attending physician.

Diagnostic testing for viral infections (primarily influenza, COVID-19) must under no circumstances delay the initiation of systemic antiviral therapy and infection control procedures.

3.1. Conservative management

3.1.1. Etiotropic (antiviral therapy)

Comments: prescribed depending on the etiology. Early administration of antiviral drugs in acute respiratory viral infections to suppress viral replication prevents severe disease progression and the risk of complications. In established CAP, rapid viral load reduction prevents severe lung damage. The appropriateness of prescribing antiviral drugs is determined by the physician individually for each patient. Regimens and doses are detailed in the treatment section of the clinical guidelines: "ARVI in adults", "Influenza in adults", and the temporary methodological recommendations "Prevention, diagnosis, and treatment of a new coronavirus infection (COVID-19)" version 18 [9 -12].

3.1.2. Pathogenetic and symptomatic therapy

Comments: Basic therapy includes bed rest, diet, and heavy fluid intake. In the absence of digestive system diseases and contraindications for a specialized diet, diet table No. 15 is indicated. The diet includes easily digestible foods rich in vitamins (lean meats, fish, dairy products, fruits, vegetables, juices, compotes). Alcohol in any form is prohibited.

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

Comments: Excessive fluid loading in viral lung injury will aggravate the patient's condition.

Administer 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 patient's severity.

Comments: the use of NSAIDs can be recommended solely for symptomatic purposes to achieve antipyretic and analgesic effects. Prescribing them as a long-term course is impractical. Furthermore, from a practical standpoint, it should be borne in mind that prescribing NSAIDs may disorient the physician in assessing the efficacy of ongoing therapy. Recommended for use: paracetamol** 500 mg–1 g up to 4 times a day (maximum daily dose – 4 g), ibuprofen** 400 mg 3 times a day (maximum daily dose – 1200 mg), combined drug forms: paracetamol in combination with ibuprofen (ibuprofen + paracetamol).

Comments: The drugs of choice are:

Dextromethorphan (included in multicomponent drugs);

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

Levodropropizine – orally, between meals, for adults and children over 12 years of age – 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

Renalgin 1–2 tablets (or 5–10 ml of oral solution) 3 times a day, independently of meals. Depending on the severity of the condition, during the first three days, the frequency of administration may 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 recommended for hereditary fructose intolerance. The efficacy and safety of the drug have not been studied in pregnant and lactating women

Comments: various mucolytic agents, including herbal medicines, may be used only in the presence of a productive cough.

Synthetic mucolytic agents:

Acetylcysteine** – orally 600 mg/day, course up to 5-7 days

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

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

Ambroxol + Sodium Glycyrrhizinate (glycyrrhizic acid trisodium salt) + Creeping Thyme herb extract (liquid thyme extract) – orally 40 ml/day (10 ml in 4 doses).

Ambroxol + Sodium glycyrrhizinate (glycyrrhizic acid trisodium salt) + Lanceleaf Thermopsis herb extract + Sodium bicarbonate – 1 tablet 3 times a day.

Comments: it is recommended to prescribe combinations of #Fenoterol and Ipratropium bromide** in the form of a metered-dose inhaler (MDI) at a dose of 50 mcg/20 mcg (1-2 puffs) up to 3-4 times a day or in the form of a nebulizer solution at a dose of 0.5 mg/ml + 0.25 mg/ml (1-2 ml) up to 3-4 times a day

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

Antibacterial drugs

The treatment of bacterial pneumonia is not covered in these guidelines and should be managed in accordance with clinical guidelines for the treatment of community-acquired pneumonia in adults!

Comments: Glucocorticosteroids (GCS) are the drugs of choice for treating patients with a cytokine storm; they suppress all phases of inflammation and the synthesis of a wide range of pro-inflammatory mediators, whose increased concentration during a cytokine storm is associated with an unfavorable prognosis in COVID-19 and the risk of developing ARDS.

For the treatment of moderate and severe viral pneumonia with respiratory failure, various GCS administration regimens can be used: #dexamethasone** at a dose of 6–20 mg/day intravenously in 1–2 administrations depending on the patient's severity; #methylprednisolone** at 125 mg/administration intravenously every 12 hours or as a single bolus of 250–500 mg/administration intravenously.

The maximum GCS dose is used for 3–4 days and then tapered upon stabilization (resolution of fever, stable decrease in CRP levels, ALT and/or AST activity, serum LDH) by 20–25% per administration/day over the first 2 days, and subsequently by 50% every 1–2 days until complete discontinuation. GCS therapy for more than 10 days is not recommended.

Patients receiving GCS must be monitored for side effects. These include hyperglycemia, arterial hypertension, and erosive and ulcerative lesions of the upper gastrointestinal tract.

GCS must be used with caution in cases of: diabetes mellitus, essential hypertension, gastric and duodenal ulcer disease, obesity, signs of an active bacterial infection, and thrombotic disorders.

Comments: upon the appearance of signs of acute respiratory failure (SpO₂ <92%), oxygen inhalation via nasal catheters or face masks must be provided. Depending on the clinical situation (degree of hypoxemia, response to oxygen therapy), various oxygen delivery systems are used: low-flow nasal cannulas (FiO₂ = 0.25–0.4); a face mask (FiO₂ = 0.35–0.5), or high-flow nasal cannulas using high-flow nasal oxygen therapy (HFNO) devices. 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 (PaO₂ >60 mm Hg, SpO₂ >92%).

Comments: The main indications for invasive mechanical ventilation are respiratory arrest, impaired consciousness, psychomotor agitation, hemodynamic disorders, the inability to ensure airway patency and a tight mask seal, a high risk of aspiration, a respiratory rate >35 breaths/min, PaO₂/FiO₂ <300 mm Hg, and an increase in PaCO₂ >20% from baseline or greater than 60 mm Hg.

Goals of respiratory support:

- Correction of gas exchange disorders (achieving PaO₂ within 55–80 mm Hg, SaO₂ – 88–95%);

- Minimization of the risk of barotrauma and volutrauma;

- Optimization of alveolar recruitment;

- Early weaning of the patient from the ventilator;

- Implementation of a set of special measures aimed at limiting the risk of virus transmission from the patient to staff and other patients.

Comments: The rapid progression of ARDS dictates the need for early contact with a center that has ECMO capabilities. ECMO is performed in departments with experience using this technology: hospitals that have specialists, including surgeons and perfusionists, proficient in cannulation techniques and ECMO setup.

Potential indications for ECMO:

- Refractory persistent* hypoxemia: PO₂/FiO₂ <50 mmHg (despite FiO₂ >0.8 + PEEP (≤20 cm H₂O) at Pplat = 32 cm H₂O + prone positioning +/- inhaled NO);

- Plateau pressure ≥35 cm H₂O (despite reducing PEEP to 5 cm H₂O and lowering Vt to the minimum value (4 mL/kg) and pH ≥7.15).

* The persistence pattern depends on the dynamics of the process (a few hours for rapidly progressive conditions and up to 48 hours in case of stabilization).

Contraindications to ECMO:

- Severe comorbid conditions with a life expectancy of no more than 5 years;

- Multiple organ failure and SAPS II >90 points or SOFA >15 points;

- Non-pharmacological coma (due to stroke);

- Inability to establish venous or arterial access;

- Body mass index >40 kg/m².

3.2. Surgical treatment

Not performed

4. Medical Rehabilitation and Sanatorium-Resort Treatment

Comments: the initial stage of rehabilitation is usually carried out in an inpatient setting and coincides with the onset of the acute phase of the disease. If necessary, initial-stage interventions are performed in the ICU. Interventions at this stage aim to prevent the development of respiratory failure, restore and maintain natural breathing, improve the drainage function of the lungs, activate respiratory muscles, normalize gas exchange and other lung tissue functions, and prevent early complications. Reflexology is not used at this stage

Comments: the developing stage of rehabilitation is aimed at restoring normal pulmonary ventilation, preventing the decline of external respiration functions, developing respiratory muscles, preventing the development of congestion, pulmonary fibrosis, and other signs of chronic pulmonary diseases

Comments: oxyethylammonium methylphenoxyacetate has both immunomodulatory and adaptogenic properties. Administer orally on the first day 3 tablets (600 mg) per day, for the subsequent 7 days 1 tablet (200 mg) per day. Total course dose is 10 tablets (total dose 2000 mg), course duration is 8 days.

Comments: Gradual increase in dosed physical and mental stress, as well as the differentiated application of various impact methods, are important.

Comments: the rate and degree of restoration of the functional state and occupationally significant functions of convalescents are taken into account (using indirect and direct methods).

Comments:

1. Inspiratory training—breathing exercises for coronavirus-induced lung damage, resulting from alveolar injury, to improve pulmonary ventilation capacity, breathing mechanics, and respiratory muscle function. The use of volume- and flow-motivated incentive spirometers is rational

2. Vibration and percussion therapy – a method combining the mechanical impact of high-frequency vibration and compression on the chest wall.

3. Intrapulmonary percussive ventilation—a method combining non-invasive mechanical ventilation, recruitment of poorly ventilated lung areas with subsequent improvement in ventilation homogeneity and normalization of ventilation-perfusion ratios, and mobilization of bronchial secretions

4. Oscillatory PEP devices—combination of preventing air trapping on expiration and mobilizing sputum

5. Prevention and Dispensary Observation

5.2. Non-specific prevention[1]

• The patient is isolated at home or, if necessary, in a hospital setting until complete clinical recovery. Focal containment measures are not carried out. It is necessary to provide the patient with separate tableware and personal care items [1-4,7].

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

• Quarantine and isolation measures for contacts are not organized [1-4,7].

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

Comments: Prescription regimens and doses are detailed in the prevention section of the clinical guidelines: "ARVI in adults", "Influenza in adults", and the interim guidelines "Prevention, diagnosis and treatment of novel coronavirus infection (COVID-19)" version 18

Non-specific prophylaxis is divided into two options: emergency prophylaxis, designed for the immediate antiviral effect of chemical agents, interferons, and interferon inducers (focal and non-focal (scheduled)), and seasonal prophylaxis performed in the pre-epidemic period to increase the human body's resistance to respiratory viruses during the period of maximum disease probability. Focal prophylaxis is carried out among individuals who have been in direct contact with patients in families, apartments, hospital rooms (epidemic foci). The duration of focal prophylaxis ranges from 2 days upon cessation of contact with the source of infection up to 5-7 days if contact persists. Non-focal prophylaxis is carried out among populations at high risk of ARVI infection and at high risk of adverse disease outcomes

5.3 Clinical follow-up (dispensary observation)

• After discharge, for 1 month, it is recommended to refrain from routine vaccinations, except (if indicated) tetanus toxoid** and rabies vaccine** [1-4,7].

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

^[1] SanPiN 3.3686-21 "Sanitary and epidemiological requirements for the prevention of infectious diseases. XXXIV. Prevention of influenza and other acute respiratory viral infections" (Decree of the Chief State Sanitary Doctor of the Russian Federation No. 2 dated January 28, 2021).

6. Organization of Medical Care

The choice of treatment tactics is influenced by the following factors [1-4,7]: patient age; nature of comorbidities; clinical form of the disease; disease course pattern (dynamics of symptom progression); disease severity; presence and nature of complications.

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

1. SpO₂ <90%

2. Progressive and pronounced dyspnea, RR >30 per minute

3. Cyanosis

4. SBP <90 mm Hg

5. CNS dysfunction (GCS score <15 points)

6. Shock (mottled extremities, acrocyanosis, cold extremities, delayed capillary refill time (>3 s), lactate >3 mmol/L

7. Hepatic dysfunction (increase in plasma bilirubin concentration >20 µmol/L for 2 days or a 2-fold or greater increase in transaminases from the normal range)

8. Acute kidney injury (hourly urine output <0.5 mL/kg/h for 1 hour or a 2-fold increase in creatinine from the normal range)

9. Coagulopathy (platelet count <100 × 10^3/µL or a 50% decrease from the peak value within 3 days)

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

Comment: certain scales will also help the anesthesiologist-resuscitator evaluate the indications for ICU admission: CURB-65, PORT, ATO/AOIB, SMART-COP.

Comments:

1) with symptoms indicating impaired oxygen supply to the body or cardiopulmonary failure (dyspnea [upon exertion or at rest], labored breathing, cyanosis, bloody or stained sputum, chest pain, hypotension; hypoxia detected by pulse oximetry);

2) with symptoms indicating CNS complications (altered mental status, unconsciousness, drowsiness or difficulty waking up, and intermittent or constant convulsions [seizures], confusion, severe weakness or paralysis);

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

4) upon the onset of severe dehydration manifested by decreased activity, dizziness, reduced diuresis, and lethargy.

Conditions for the provision of medical services

Medical care is provided in the following forms:

• emergency medical care;

• urgent 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 primary health care is provided by an infectious disease specialist of a medical organization providing medical care to outpatients.

Specialized, including high-tech, medical care is provided in an inpatient setting by infectious disease specialists and other medical specialists and includes the prevention, diagnosis, and 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.

^[1] SanPiN 3.3686-21 "Sanitary and epidemiological requirements for the prevention of infectious diseases. XXXIV. Prevention of influenza and other acute respiratory viral infections" (Resolution of the Chief State Sanitary Doctor of the Russian Federation No. 2 dated January 28, 2021).

^[2] Letter of the Federal Service for Surveillance on Consumer Rights Protection and Human Welfare of the Russian Federation No. 01/17863-9-32 dated November 26, 2009, "On forwarding the WHO document 'Clinical management of human infection with pandemic influenza A (H1N1) 2009 virus'".

7. Additional Information

The severity of viral pneumonia and the mortality rate are higher in patients older than 65 years and individuals in risk groups:

• women of childbearing age (due to pregnancy and breastfeeding, leading to iron and micronutrient deficiency or decreased physical activity and obesity);

• people with severe chronic diseases (bronchopulmonary, cardiovascular, endocrine), morbid obesity (BMI ≥40 kg/m²), alcoholism;

• people with immunodeficiencies or receiving immunosuppressive therapy;

• individuals in contact with a large number of people;

• patients from closed collectives (boarding schools, social care facilities)—among members of organized adult communities with shared living quarters.

Criteria for Evaluating the Quality of Medical Care

References

Appendix A1. Working Group Composition

1. Avdeev S.N. − MD, Professor, Full Member of the Russian Academy of Sciences, Director of the National Medical Research Center for Pulmonology; Head of the Department of Pulmonology, N.V. Sklifosovsky Institute of Clinical Medicine, I.M. Sechenov First Moscow State Medical University;

2. Aleksandrovich Yu.S. − Chief freelance pediatric specialist anesthesiologist-resuscitator of the Northwestern Federal District of the Russian Ministry of Health, Head of the Department of Anesthesiology, Intensive Care and Emergency Pediatrics at the Faculty of Postgraduate and Additional Professional Education, Saint Petersburg State Pediatric Medical University of the Russian Ministry of Health, Professor, MD, Honored Scientist of the Russian Federation.

3. Babak S.L. − MD, Associate Professor, Professor at the Department of Phthisiology and Pulmonology, N.A. Semashko Research Institute of Clinical Medicine, Russian University of Medicine of the Ministry of Health of the Russian Federation

4. Gorelov A.V. − Full Member 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.

5. Zaitsev A.A. – MD, Professor, Chief Pulmonologist at the Main Military Clinical Hospital named after Academician N.N. Burdenko of the Ministry of Defense of the Russian Federation; Russian Medical Academy of Continuous Professional Education of the Russian Ministry of Health.

6. Makarevich A.M. – PhD in Medicine, Associate Professor at the Department of Therapy and Preventive Medicine, Krai State Budgetary Educational Institution of Additional Professional Education "Institute for Advanced Training of Healthcare Specialists" of the Ministry of Health of Khabarovsk Krai.

7. Malyavin A.G. − MD, 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 Respiratory Medicine Center.

8. Novak K.E. − PhD in Medicine, Associate Professor, Associate Professor at the Department of Infectious Diseases in Adults and Epidemiology, Saint Petersburg State Pediatric Medical University of the Russian Ministry of Health

9. Povtoreyko A.V. − PhD in Medicine, Chief Physician of the Pskov Regional Infectious Diseases Hospital.

10. Pozdnyakova M.G. − PhD in Medicine, Senior Researcher at the Laboratory for Testing New Protective Agents Against Viral Infections, Smorodintsev Research Institute of Influenza of the Russian Ministry of Health

11. Usenko D.V. − MD, Head of the Educational Center, Leading Researcher at the Clinical Department of Infectious Pathology, Central Research Institute of Epidemiology of Rospotrebnadzor

12. Chulanov V.P. − MD, 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

13. Esaulenko E.V. − MD, Professor, Head of the Department of Infectious Diseases in Adults and Epidemiology, Saint Petersburg State Pediatric Medical University of the Russian Ministry of Health

All working group members are members of the National Association of Experts in Infectious Diseases named after Academician V.I. Pokrovovsky (NAEID) or the Russian Scientific Medical Society of Internal Medicine (RSMSIM)

There is no conflict of interest.

Appendix A2. Methodology for Developing Clinical Guidelines

Target audience of the clinical guidelines:

1. Infectious disease physician;

2. Pulmonologist;

3. General practitioner / Internist;

4. General practitioner;

5. Medical students, clinical residents, postgraduates.

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

Determination of levels of evidence and grades of recommendation for diagnostic interventions

Table A1 – Levels of evidence certainty for diagnostic interventions

¹ The generally accepted standard for diagnostic intervention clinical trials is a cross-sectional study design, in which the investigational diagnostic method and the reference method—serving as the "gold standard" for diagnosing the studied disease or condition—are applied to each included patient in parallel and under identical conditions. The investigational and reference methods must be applied independently of each other (i.e., the investigational method cannot be part of the reference method) and must be interpreted by the investigator without knowledge of the results obtained from the other method (blinding is recommended)

Table А2 – Scale for determining the level of reliability of evidence (LRE) for diagnostic interventions

Table P3 – Possible combinations of LCE and LCR for diagnostic interventions

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

Determination of the levels of credibility of evidence and grades of recommendation for therapeutic, rehabilitation, and preventive interventions

Table S4 – Levels of evidence (LoE) for therapeutic, rehabilitative, and preventive interventions

Table P5 – Scale for determining the grades of recommendation for therapeutic, rehabilitation, and preventive interventions

Procedure for updating clinical guidelines

Clinical guidelines are updated every 3 years.

Appendix A3. Reference Materials

These clinical guidelines were developed taking into account the following regulatory legal 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, "On the Fundamentals of Protecting the Health of Citizens in the Russian Federation".

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

5. Order of the Ministry of Health and Social Development of Russia 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 Ministry of Health of the Russian Federation No. 205n dated May 2, 2023, "On Approval of the Nomenclature of Positions of Medical Workers and Pharmaceutical Workers"

8. Order of the Ministry of Health of Russia 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 and Social Protection of the Russian Federation No. 585n dated August 27, 2019, "On the Classification and Criteria Used in Medical and Social Expertise of Citizens by Federal State Institutions of Medical and Social Expertise."

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

11. SanPiN 3.3686-21 "Sanitary and epidemiological requirements for the prevention of infectious diseases." XXXIV. Prevention of influenza and other acute respiratory viral infections (Resolution of the Chief State Sanitary Doctor of the Russian Federation No. 4 dated January 28, 2021).

12. Letter of the Ministry of Health of the Russian Federation dated December 2, 2022, No. 30-4/I/1-20714. Guidelines for medical workers on the differential diagnosis of COVID-19 with influenza and ARVI, and determining management tactics for patients, including children, the elderly, and pregnant women.

13. Letter of the Ministry of Health of the Russian Federation No. 30-4/I/2-2702 dated March 6, 2020, "On Sending the Algorithm for Providing Medical Care to the Adult Population with Community-Acquired Pneumonia"

14. Order of the Ministry of Health of the Russian Federation No. 330 dated August 5, 2003, "On Measures to Improve Clinical Nutrition in Medical and Preventive Treatment Facilities of the Russian Federation."

15. Order of the Ministry of Health of the Russian Federation No. 395n dated June 21, 2013, "On Approval of Medical Nutrition Standards."

16. 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 Clinical Nutrition"

Criteria for determining the severity of pneumonia

Differential features between viral pneumonia and bacterial pneumonia. [62].

Appendix B. Physician Action Algorithms

Appendix C. Patient Information

Viral pneumonia is an acute disease characterized by inflammation developing in the lungs. This inflammation is caused by respiratory viruses, most commonly following an acute respiratory viral infection (ARVI). Sometimes viruses and bacteria can be detected in patients with pneumonia simultaneously. Pneumonia is classified as community-acquired if it develops outside of a hospital or other healthcare facility.

Microorganisms usually enter the lungs via the respiratory tract (trachea, bronchi). However, pneumonia develops only if the human body fails to eliminate the potential pathogen in a timely manner (e.g., weakened immunity, a large load of pathogens entering the lungs) or if the pathogen is highly virulent. Pneumonia can occur at any age, but it is more common in older adults (especially those over 65 years old) and in individuals with chronic comorbidities such as heart failure, diabetes mellitus, or chronic obstructive pulmonary disease. Risk factors contributing to the development of pneumonia include hypothermia, smoking, alcohol abuse, and the use of immunosuppressant medications.

As a result of inflammation, secretions accumulate in the lungs, which can impair oxygen and carbon dioxide exchange and lead to dyspnea (difficulty breathing). In pneumonia, inflammation frequently spreads to the bronchi, causing cough and sputum production, as well as the pleura (the serous membrane covering the lungs). This is accompanied by chest pain during coughing and breathing. In most patients, pneumonia is accompanied by fever (usually above 38⁰C), chills, asthenia, fatigue, and heavy night sweats. The disease may be preceded by cold symptoms (sore throat, runny nose, etc.). Pneumonia, in turn, can worsen the course of existing chronic conditions.

Pneumonia is a serious disease that, if diagnosed untimely or treated improperly, can lead to complications and even death. Therefore, if you suspect you have pneumonia, you should consult a doctor immediately.

Various methods are used to diagnose pneumonia. If pneumonia is suspected, your doctor will take a detailed history, perform a physical examination, and auscultate (listen to) your lungs using a special device. Additional tests will be ordered (usually blood tests), and if you are treated in a hospital, you may be asked to collect sputum for analysis to identify the causative microorganism. To confirm lung lesions and assess their extent, a chest X-ray or computed tomography (CT) scan will be performed.

After establishing the diagnosis, the doctor will determine the nature and severity of the pneumonia, decide whether you should be treated on an outpatient basis or in a hospital, and prescribe treatment.

In pneumonia, it is also recommended to temporarily limit excessive physical activity and drink an adequate amount of fluids.

To prevent pneumonia, it is important to follow general health-promoting measures, such as smoking cessation, regular physical activity, and adequate, balanced nutrition. Some patients at high risk for complications from influenza or coronavirus infection will be offered annual vaccination to prevent influenza and COVID-19, and patients with a high likelihood of developing severe pneumococcal infections will be offered pneumococcal vaccination.

The key to successful treatment of pneumonia is disciplined and full compliance with the doctor's recommendations and prescriptions.

How to protect yourself against respiratory infections:

1. Avoid hypothermia. It is especially important to keep your feet warm and avoid breathing cold 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 freezing weather while intoxicated or drink hot beverages right before going out, as this promotes hypothermia. You should also avoid going outside while heavily sweating. Avoid prolonged exposure to direct airflow from air conditioners and drafts.

2. Avoid close contact with individuals suffering from ARVI. Do not share tableware.

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

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

5. Chemoprophylaxis.

If you fall ill, 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

Appendix G1. Scales and algorithms for assessing prognosis and severity of VP

Russian title: PORT (PSI) Scale

Original title: PORT (Pneumonia Outcomes Research Team) Scale or Pneumonia Severity Index (PSI)

Source (validated publication): Fine M., Auble T., Yealy D. et al. A prediction rule to identify low risk patients with community acquired pneumonia. N. Engl. J. Med. 1997; 336 (4): 243–250.

Type (underline):

scale

assessment index

questionnaire

other (specify)

Purpose: assessment of the risk of adverse outcome in community-acquired pneumonia (CAP). Content (template):

Algorithm for assessing the risk of an adverse prognosis

Table 1. Scoring of risk factors for an adverse prognosis

Table 2. Risk classes and clinical profile of a patient with CAP

Key (interpretation): the scale includes 20 clinical, laboratory, and radiological signs of CAP. The risk class is determined by stratifying the patient into one of five groups. This uses a two-step scoring system based on the analysis of prognostic-significant demographic, clinical, laboratory, and radiological parameters.

During the development and subsequent validation of the scale, researchers established that mortality rates are: for class I – 0.1-0.4%; class II – 0.6-0.7%; class III – 0.9-2.8%; class IV – 8.5-9.3%; class V – 27.0-31.1%

Notes: CAP is generally associated with an unfavorable prognosis; accordingly, it is important to assess the risk of death in patients.

Appendix G2. CURB/CRB-65 Scale.

Russian name: CURB/CRB-65 scale

Original name: CURB-65 (confusion, urea, respiratory rate, blood pressure); CRB-65 (confusion, respiratory rate, blood pressure)

Source (validated publication):

• Lim W., van der Eerden M., Laing R. et al. Defining community acquired pneumonia severity on presentation to hospital: an international derivation and validation study. Thorax. 2003; 58 (5): 377– 382.

• Bauer T., Ewig S., Marre R. et al. CRB-65 predicts death from community acquired pneumonia. J. Intern. Med 2006; 260 (1): 93–101.

Type (underline):

assessment scale

index

questionnaire

other (specify)

Purpose: assessment of the risk of adverse outcome in CAP

Content (template):

I. Algorithm for assessing the risk of unfavorable prognosis and choosing the site of care in CAP using the CURB-65 scale

II. Algorithm for assessing the risk of unfavorable prognosis and choosing the site of care in CAP using the CRB-65 scale

Key (interpretation): an approach to assessing the risk of adverse outcome in CAP involving the analysis of five signs:

• altered mental status caused by pneumonia;

• blood urea nitrogen >7 mmol/L (for the CURB-65 scale only);

• tachypnea ≥30/min;

• decrease in systolic blood pressure (BP) <90 mm Hg or diastolic ≤60 mm Hg;

• patient age ≥65 years.

The presence of each sign is scored as 1 point. The total score can range from 0 to 5 points, with the mortality risk increasing as the total score rises. CRB-65 is characterized by the absence of the laboratory parameter blood urea nitrogen in the evaluation criteria, which simplifies the use of this scale in outpatients and in the emergency department of a medical organization

Notes: The CURB/CRB-65 scales are of high importance in assessing the risk of death and choosing the site of care for patients with CAP.

Appendix G3. IDSA/ATS Severe CAP Criteria, 2007.

Russian name: IDSA/ATS Severe CAP Criteria, 2007

Original name: 2007 Infectious Diseases Society of America/American Thoracic Society Criteria for Defining Severe Community-acquired Pneumonia

Source (validation publication):

• Mandell LA, Wunderink RG, Anzueto A, et al. American Thoracic Society. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. 2007;44:S27–S72.

• Brown SM, Jones BE, Jephson AR, et al. Validation of the Infectious Disease Society of America/American Thoracic Society 2007 guidelines for severe community-acquired pneumonia. Crit Care Med. 2009;37:3010–3016.

• Phua J, See KC, Chan YH, et al. Validation and clinical implications of the IDSA/ATS minor criteria for severe community-acquired pneumonia. Thorax. 2009;64:598–603

• Chalmers JD, Taylor JK, Mandal P, et al. Validation of the Infectious Diseases Society of America/American Thoracic Society minor criteria for intensive care unit admission in community- acquired pneumonia patients without major criteria or contraindications to intensive care unit care. Clin Infect Dis. 2011;53:503–511

Type (underline):

rating scale

index

questionnaire

other (specify)

Purpose: identification of patients with severe CAP who require urgent hospitalization in the ICU by evaluating "major" and "minor" criteria associated with increased mortality

Content (template):

IDSA/ATS Severe CAP Criteria, 2007

¹ additional criteria – hypoglycemia (in patients without diabetes mellitus), hyponatremia, metabolic acidosis/elevated lactate unexplained by other causes, cirrhosis, asplenia, alcohol overdose/sudden withdrawal in dependent patients

² blood urea nitrogen (mg/dL) = urea (mmol/L) * 2.8

Key (interpretation): The IDSA/ATS algorithm is based on two "major" and nine "minor" criteria associated with increased mortality in CAP. The presence of one "major" or three "minor" criteria is an indication for patient admission to the ICU. When making a decision, especially in borderline situations, additional criteria can be taken into account along with the nine "minor" criteria (see above).

Notes: The IDSA/ATS severe CAP criteria help identify patients with severe CAP and assess the need for their transfer to the ICU.

Appendix G4. SMART-COP/SMRT-CO Scale.

Russian name: SMART-COP/SMRT-CO Scale

Original name: SMART-COP (systolic blood pressure, multilobar infiltration, albumin, respiratory rate, tachycardia, confusion, oxygenation, pH); SMRT-CO (systolic blood pressure, multilobar infiltration, respiratory rate, tachycardia, confusion, oxygenation); Source (validation publication):

• Charles P., Fine M., Ramirez J. et al. Validation of SMART-COP: a pneumoniae severity assessment tool for predicting with patients will need intensive respiratory or inotropic support (IRIS). In: 47th ICAAC. Chicago; 2007:Abstr: L1156a.

• Charles P., Wolfe R., Whitby M. et al. SMART-COP: A tool for predicting the need for intensive respiratory or vasopressor support in community-acquired pneumonia. Clin. Infect. Dis. 2008; 47 (3): 375–384.

• Chalmers J., Singanayagam A., Hill A. Predicting the need for mechanical ventilation and / or inotropic support for young adults admitted to the hospital with community-acquired pneumonia. Clin. Infect. Dis. 2008; 47 (12):1571–1574.

Type (underline):

rating scale

index

questionnaire

other (specify)

Purpose: assessment of CAP severity by identifying patients requiring intensive respiratory support and vasopressor infusion to maintain adequate blood pressure

Content (template):

1. Parameters evaluated in the SMART-COP/SMRT-CO scale

* Not evaluated in the SMRT-CO scale

2. SMART-COP Interpretation

3. SMRT-CO Interpretation

Key (Interpretation): The SMART-COP score provides a point-based evaluation of clinical, laboratory, physical, and radiological signs to determine the probabilistic need for intensive care treatments: respiratory support and vasopressors. The modified SMRT-CO version does not require the assessment of parameters such as albumin level, PaO2, and arterial blood pH. The risk of requiring mechanical ventilation or vasopressors according to the SMART-COP scale is high with 5 or more points, and according to the SMRT-CO scale, with 3 or more points.

Notes: The SMART-COP/SMRT-CO score allows assessing the need for patient admission to the ICU.