Coronavirus (COVID-19) and Galavit: possible benefits in treatment

Detailed description of the study

In the modern world, more and more patients with chronic infectious diseases are registered every day. For treatment, drugs have been developed that affect not only the pathogen itself (virus, bacteria, fungi), but also the human body to activate the immune system, such drugs include immunomodulators.

Immunomodulators are substances that can increase the activity of the immune system to fight pathogenic organisms (bacteria, viruses, fungi). These drugs are prescribed to correct the functioning of the immune system in complex treatment. Galavit is a synthetic drug that belongs to the immunomodulators and also has an anti-inflammatory effect, the active ingredient of which is aminophthalhydrazite. The mechanism of action of this drug is due to its ability to interact with blood cells (phagocytes, monocytes, neutrophils, macrophages, natural killer cells) to combat pathogenic organisms. Side effects when taking it are rare. This drug is used in children over 12 years of age and adults in the form of tablets or suppositories (suppositories). It is used in complex therapy of many diseases and conditions, including:

1. acute respiratory infections;
2. diseases of the ENT organs (tonsillitis, otitis media, etc.);
3. inflammation of the mouth and gums;
4. diseases caused by the herpes virus;
5. infectious and non-infectious diseases of the genitourinary system and pelvic organs
6. pathology of the gastrointestinal tract;
7. asthenia, increased fatigue
8. postoperative complications and their prevention.

Galavit indirectly affects the stimulation of interferons (alpha and gamma), promoting the activation of the human immune system. Interferons are a family of protein molecules that belong to cytokines; they actively participate in the immune system to fight pathogenic microorganisms. They regulate intercellular interactions, cell growth and reproduction, and participate in the coordination of innate and acquired immunity.

There are several types of interferons:

• Interferon alpha - produced by leukocytes, participates in the fight against pathogenic microorganisms.
• Interferon beta - produced in fibroblasts, its function is similar to interferon alpha.
• Interferon gamma is synthesized by immune blood cells: T-lymphocytes and so-called killer T-cells. Its function is to have an immunomodulatory and antitumor effect on the cells of the body.

In order to understand how effective treatment with Galavit will be in a patient, especially if the drug is prescribed for a long time, it is necessary to assess sensitivity to it, that is, the body’s ability to produce interferons in response to taking the drug.

The more interferons released, the stronger the immune system's response to this drug and the more effective the treatment.

General information

Trade name Galavit®
Registration number LSR-008746/09

INN or group name Aminodihydrophthalazindione sodium

Chemical name 5-amino-1,2,3,4-tetrahydrophthalazine-1,4-dione sodium salt

Dosage form Sublingual tablets

Release form

Sublingual tablets, 25 mg. 10 or 20 sublingual tablets in blister packs made of polyvinyl chloride film and aluminum foil. 1, 2, 3 or 4 contour packages along with instructions for use in a cardboard box. 10, 20, 30, 40 or 50 contour packs with an equal number of instructions for use in a group pack

Compound

Active ingredient - sodium aminodihydrophthalazindione (Galavit®) 0.025 g, excipients - sorbitol 0.315 g, starch 0.14 g, lactose 0.1 g, calcium stearate 0.005 g, talc 0.015 g and racementol (menthol) 0.0001 g. Description The tablets are white with a yellowish tint, biconvex, without a score, with a menthol odor.

Pharmacotherapeutic group

Immunomodulatory and anti-inflammatory agent.

ATX code L03

Pharmacological properties

Pharmacodynamics

The mechanism of action of the drug is associated with its ability to regulate the functional and metabolic activity of innate and adaptive immune cells (monocytes, macrophages, neutrophils, natural killer cells, etc.). Galavit normalizes the phagocytic activity of monocytes/macrophages, the bactericidal activity of neutrophils and the cytotoxic activity of NK cells. At the same time, by restoring the reduced activity of innate and adaptive immune cells, the drug increases the body’s resistance to infectious diseases of bacterial, viral and fungal etiology, promotes faster elimination of the pathogen from the body, and reduces the frequency, severity and duration of infections.

In addition, Galavit normalizes antibody formation, increases the functional activity (affinity) of antibodies, and indirectly regulates the production of endogenous interferons (IFN-α, IFN-γ) by producer cells. In inflammatory diseases, the drug reversibly inhibits for 6-8 hours the excessive synthesis of tumor necrosis factor-α, interleukin-1, interleukin-6 and other pro-inflammatory cytokines by hyperactivated macrophages, the level of which determines the degree of inflammatory reactions, their cyclicity, as well as the severity of intoxication of the body.

Galavit reduces the production of reactive oxygen species by hyperactivated macrophages, thereby reducing the level of oxidative stress and protecting tissues and organs from the destructive effects of radicals. Normalization of excessively increased functional activity of phagocytic cells leads to the restoration of their antigen-presenting and regulatory functions, and a decrease in the level of autoaggression. The drug is well tolerated and has no allergenic, mutagenic, embryotoxic, teratogenic or carcinogenic effects. Pharmacokinetics Excreted from the body mainly through the kidneys. When administered sublingually, the half-life is 30 minutes. The main pharmacological effects are observed within 72 hours.

Russia, 123290, Moscow, dead end Magistralny 1st, 5A, room. 91 Tel/fax 8-800-707-71-81 E-mail: [email protected] ; https://www.galavit.ru Address of production site 308013, Belgorod, st. Rabochaya, 14 Send claims to the address 123290, Moscow, dead end Magistralny 1st, 5A, room. 91. Tel. 8-800-707-71-81

Indications for use

In adults and adolescents over 12 years of age (including those with secondary immune deficiency) as an immunomodulatory and anti-inflammatory agent in complex therapy:

• acute respiratory infections, diseases of the respiratory tract and ENT organs (including often recurrent ones) of bacterial and viral etiology (ARVI, influenza, bronchitis, pneumonia, tonsillitis, otitis, adenoiditis) and their prevention;
• inflammatory diseases of the mucous membrane of the mouth and throat, periodontal diseases;
• chronic recurrent diseases caused by the herpes virus;
• decreased physical performance (including among athletes)

Directions for use and doses

Sublingually, 1 tablet up to 4 times a day or 2 tablets up to 2 times a day.

• For acute respiratory infections, flu, bronchitis, pneumonia, tonsillitis, otitis, adenoiditis for treatment: 1 tablet 4 times a day. Course 5 days.
• In case of chronic and frequent relapsing course, continue 1 tablet 4 times a day every other day for a course of up to 15 days.
• For prevention: 1 tablet 2 times a day. Course 5-10 days.
• For inflammatory diseases of the mucous membrane of the mouth and throat, periodontal diseases: 1 tablet 4 times a day for 5 days. Then 1 tablet 4 times a day after 3 days for a course of up to 3 weeks.
• For chronic recurrent diseases caused by the herpes virus: 1 tablet 4 times a day for 10 days. Then 1 tablet 4 times a day every other day for 10 days.
• To increase physical performance: 1 tablet 4 times every other day for 10 days, then 1 tablet 4 times a day after 3 days for a course of up to 3 weeks.

Treatment with Galavit can be started at any stage of the disease. Use the drug according to the indications, the method of administration and in the doses indicated in the instructions. If after these courses of treatment there is no improvement, or the symptoms worsen, or new symptoms appear, you should consult your doctor.

Precautionary measures

Contraindications

Individual intolerance, intolerance to galactose, fructose, lactase deficiency or glucose-galactose malabsorption, pregnancy and breastfeeding, children under 12 years of age.

Use during pregnancy and breastfeeding

The drug is contraindicated for pregnant women and women during breastfeeding.

Side effects

In rare cases, allergic reactions are possible. If you experience the side effects listed in the instructions or they get worse, or you notice any other side effects not listed in the instructions, tell your doctor.

Overdose

No cases of overdose have been reported.

Interaction with other drugs

With simultaneous use, it is possible to reduce the course doses of antibiotics. Galavit allows you to increase the effectiveness of antibiotic therapy and reduce its damage

The drug contains sorbitol; patients with rare hereditary pathologies associated with fructose and sorbitol intolerance should not take the drug.

Impact on the ability to drive vehicles and machinery

The drug does not affect the ability to drive vehicles or operate machinery.

Shelf life, storage conditions

Storage conditions: Store at a temperature not exceeding 25 ° C, in a place protected from light. Keep out of the reach of children.

Shelf life: 3 years. Do not use after the expiration date indicated on the carton.

Conditions for dispensing from pharmacies Dispensed without a prescription.

What else is prescribed with this study?

Immune status (screening) (Phagocytic activity of leukocytes, cellular immunity, total immunoglobulin IgE, immunoglobulins IgA, IgM, IgG)

27.960. Ven. blood 3 days

7,640 ₽ Add to cart

Immune status expanded

17.61. Ven. blood 14 days

22 310 ₽ Add to cart

Cellular immunity (T-lymphocytes, T-helpers, T-cytotoxic cells, Immunoregulatory index, B-lymphocytes, NK-T cells, NK cells, Leukocyte formula)

17.50. Ven. blood 3 days

5 200 ₽ Add to cart

Clinical studies of Galavit for COVID-19

For 2021, 2 small clinical studies of Galavit for coronavirus infections are known (if you know more, please tell us in the comments):

1. Prevention of moderate and severe forms of COVID-19 with Galavit among medical personnel in the “red zone” (June 2020): symptoms of coronavirus infection occurred in 6.4%
   of medical workers in the “red zone” who took Galavit, and in
   17.6%
   of those who did not, the difference was statistically reliable;
2. (PDF) Use of Galavit to prevent the progression of pneumonia in COVID-19 (Therapeutic archive 11, 2020): 22 patients with
   moderate to severe COVID pneumonia with an average age of 62 years and lung damage according to CT from 25 to 75% in the second week from At the onset of the disease, Galavit was added to the treatment. In all patients, shortness of breath and acrocyanosis quickly decreased, and there were positive changes in CT and laboratory parameters. No one needed a ventilator, and no one died.

Unfortunately, these studies are small, therefore, from a Western point of view, Galavit should be classified as drugs with unproven effectiveness. However, doctors who have worked with this drug have good reviews of it. For influenza, Galavit lowered the temperature and accelerated recovery, also eliminating asthenic syndrome (a feeling of weakness after an infection).

References

1. Sologub T.V., Osinovets O.Yu. Use of the immunomodulatory drug Galavit in the complex therapy of influenza // Clinician. 2012. No. 2.
2. Ermishina V.I., Kazeko N.I., Oskolkov S.A. Results of using the immunomodulatory drug “Galavit” for complicated chronic pyelonephritis and urolithiasis // Tyumen Medical Journal. 2015. No. 3.
3. Silin DS, Lyubomska OV, Ershov FI, Frolov VM, Kutsyna GA. Synthetic and natural immunomodulators acting as interferon inducers. Curr Pharm Des. 2009;15(11):1238-47. doi: 10.2174/138161209787846847. PMID: 19355963.
4. da Silva EG, Gionfriddo JR, Hudachek SF, Gustafson DL, Olea-Popelka FJ, Scofield VL, Powell CC, Hill AE. Evaluation of the ocular penetration of topical alpha-luminol (Galavit®/GVT®). Vet Ophthalmol. 2011 May;14(3):180-5. doi: 10.1111/j.1463-5224.2010.00862.x. PMID: 21521442.

Galavit

The dosage regimen and duration of therapy are set individually depending on the nature and severity of the disease, as well as the age of the patient.

To prepare a solution for intramuscular injection, the drug in the form of a powder for preparing a solution for injection is diluted in 2 ml of water for injection or in 0.9% sodium chloride solution.

Adults and adolescents over 12 years of age (in complex therapy of immunodeficiency conditions)

For peptic ulcer of the stomach and duodenum in the acute period - 2 days, 200 mg 1 time / day, then 100 mg at intervals of 72 hours. A course of 15-25 injections. In the chronic period - for 5 days, 100 mg 1 time / day, then - 100 mg every 72 hours. Course - 20 injections.

For viral hepatitis, the initial dose is 200 mg once, then 100 mg 2 times a day until the symptoms of intoxication and inflammation subside. Subsequent continuation of the course of therapy at a dose of 100 mg with an interval of 72 hours. The course is 20-25 injections.

For chronic recurrent herpes infection, the drug is prescribed 100 mg daily for 5 injections, then 100 mg every other day for 15 injections.

For diseases caused by the human papillomavirus, the drug is prescribed for 5 days at 100 mg 1 time / day, then 100 mg every other day. The course is 20 injections.

For urogenital infections (chlamydial and trichomonas urethritis, chlamydial prostatitis), the drug is prescribed at 100 mg 2 times a day on the 1st day, then switched to administering the drug at 100 mg every other day. The course is 10-15 injections, depending on the severity of the pathological process.

For salpingoophoritis and endometritis in the acute period, the drug is prescribed for 2 days at 200 mg 1 time / day, then 100 mg at intervals of 72 hours. The course is 20 injections. In the chronic period, the drug is prescribed for 5 days, 100 mg 1 time/day, then 100 mg every 72 hours. The course is 20 injections.

For acute and chronic inflammatory diseases of the pelvic organs in the acute period, the drug is prescribed on the 1st day 200 mg once, then for 3 days 100 mg daily, then 100 mg every other day for 5 injections. Course - 10 injections. In the chronic period, the drug is prescribed for 5 days, 100 mg 1 time/day, then 100 mg every 72 hours. The course is 20 injections.

For postoperative rehabilitation of patients with uterine fibroids and for complications of the postoperative period in patients of reproductive age, the drug is prescribed for 5 days, 100 mg 1 time/day, then 100 mg every other day. The course consists of 15 injections.

For the prevention and treatment of surgical complications in the preoperative and postoperative period (including in cancer patients), the drug is prescribed at a dose of 100 mg 1 time/day. Before surgery, 5 injections, after surgery, 5 injections of 100 mg every other day and 5 injections of 100 mg with an interval of 72 hours. For severe disease, the initial dose is 200 mg 1 time / day or 100 mg 2 times / day. Course - 20 injections.

For chronic recurrent furunculosis and erysipelas, 100 mg of the drug is prescribed once a day for 5 days, then 100 mg every other day. Course - 20 injections.

For asthenic conditions, neurotic and somatoform disorders, for mental, behavioral and post-withdrawal disorders, alcohol and drug addiction, the drug is prescribed for 5 days, 100 mg 1 time / day, then 100 mg every 72 hours. The course is 15-20 injections .

To increase physical performance, the drug is prescribed 100 mg every other day for 5 injections, then 100 mg every 72 hours. The course is up to 20 injections.

For inflammatory diseases of the mucous membrane of the oral cavity and pharynx, periodontal diseases, the initial dose is 100 mg daily for 5 injections, then 100 mg at intervals of 72 hours. The course is 15 injections.

Adults and adolescents over 12 years of age (as monotherapy)

For acute and chronic infectious and inflammatory diseases of the gastrointestinal tract, accompanied by intoxication and/or diarrhea, 200 mg is prescribed once, then 100 mg 2 times a day until the symptoms of intoxication are relieved. It is possible to subsequently continue the course of 100 mg at intervals of 72 hours. The course is 20-25 injections.

For chronic infectious and inflammatory diseases of the urogenital tract, incl. when carrying out immunorehabilitation measures during the inter-relapse period, in order to maintain clinical remission, 100 mg is prescribed every other day. Course - 10 injections.

Children over 6 years of age

For purulent surgical diseases (including burn lesions, recurrent furunculosis, chronic osteomyelitis, gangrenous appendicitis with omentitis, peritonitis, purulent pleurisy), the drug is prescribed to children aged 6 to 11 years - 1 injection of 50 mg 1 time per day. for 5 days, then 1 injection of 50 mg every other day for 10-15 days. The course is 10-15 injections. Children and adolescents aged 12 to 18 years are treated according to the same regimen in the form of intramuscular injections of 100 mg.

When dressings, it is desirable to apply Galavit externally in the form of dressings with sterile napkins moistened with a 1% solution of Galavit in water for injection (in dressings with mash or water-soluble ointment dressings).

For frequent recurrent diseases of the respiratory tract and ENT organs of bacterial and viral etiology (frequent acute respiratory viral infections, bronchitis, pneumonia, chronic tonsillitis, chronic otitis, chronic adenoiditis) for children aged 6 to 11 years, the drug is prescribed 1 injection of 50 mg 1 time / day for 5 days, then 50 mg 1 time/day every other day for 10-15 days. The course is 10-15 injections. Children and adolescents aged 12 to 18 years are treated according to the same regimen in the form of intramuscular injections of 100 mg.

Overdose

To date, no cases of overdose of the drug Galavit® have been reported.

Scientists' opinions and doctors' reviews about Galavit

Filatov Nikolay Nikolaevich

, Deputy Director of the Research Institute of Vaccines and Serums named after I. I. Mechnikov (Moscow), April 20, 2020 at a meeting on the sanitary and epidemiological situation in the Russian Federation:

There are many scientific studies that have proven the high effectiveness of Tamerit in these situations. This is a drug called “Galavit”. It had approved instructions for use and was approved for use for medical purposes. Now, however, these documents are already outdated. But scientific research has shown its high effectiveness. Perhaps it is now necessary to conduct an evaluation and, as part of a clinical trial, evaluate the effectiveness of this drug and, possibly, include it in the treatment regimen of patients.

Kolesov Sergey Vasilievich

, head of the department of spine pathology at the Central Research Institute of Traumatology and Orthopedics named after N. N. Priorov (Moscow) on April 24, 2021, addressed from his Instagram account:

Current issues of severe herpetic infection in adults

Currently, the number of patients with recurrent herpes infection caused by herpes simplex viruses (HSV) types 1 and 2 of various localizations is steadily increasing. The most common localization in adults is anogenital and labial. Many issues of the pathogenesis and treatment of severe and extremely severe herpesvirus infection are still not resolved.

The HSV species belongs to the family Herpesviridae, subfamily L-Herpesviridae, a species of HSV. There are two main types of virus - HSV 1 and HSV 2. Infection is possible with either one or two types of pathogen. HSV is capable of invading various cells of the human body: skin cells, mucous membranes of the urogenital and gastrointestinal tracts (GIT), respiratory tract, central and peripheral nervous system, liver, vascular endothelium, as well as blood cells - lymphocytes, etc. [ 1]. The place of permanent residence (lifelong persistence) of HSV is the paravertebral sensory ganglia. HSV is transmitted by direct contact; the pathogen can be transmitted through household contact and vertical routes (from mother to fetus), as well as through transfusion and parenteral routes through instruments during surgical interventions, dental procedures, etc.

As you know, most people are infected with HSV. The primary immune response to infection occurs latently or with herpetic eruptions with a local and general inflammatory reaction. In individuals with a normal immune response, HSV multiplication (replication) is under immunological control, and relapses are extremely rare or do not occur throughout life. The antiviral defense of the body involves nonspecific defense factors that destroy or block viruses: macrophages and other cells producing interferons (IFN) α, β and γ, a number of interleukins (IL) (tumor necrosis factor (TNF), IL-6, etc.) , natural killer cells and factors that form a specific immune response against a particular virus: cytotoxic T lymphocytes (CTL) (CD8+ T lymphocytes) and B lymphocytes, responsible for the production of specific antibodies that block the replication of the virus and viruses located outside the cell. For adequate functioning of these cells and maintaining the immune response, appropriate production of IFN and IL is necessary.

Under the influence of various exogenous and endogenous factors that damage the immune system, control over viral replication may weaken and, accordingly, the development of relapse. Recurrence of HSV infection can be triggered by other infectious diseases, hypothermia, excessive insolation, mental or physical stress, intoxication of various origins, including alcohol consumption, cyclical changes in hormonal status (menstruation), especially with an imbalance of hormone levels in women, sudden changes in climatic zones and etc.

With long-term chronic infection, viruses have a multifaceted adverse effect on the human immune system. HSV directly damages cells of the immune system (lymphocytes, macrophages and natural killer cells). By synthesizing suppressor proteins and chimeric proteins, viruses inhibit many immune reactions: HSV can block the action of IFN, disrupt the recognition of infected cells and other protective reactions. In addition, the high mutational activity of the viral genome also contributes to the escape of the virus from immunological control.

Chronic, often recurrent HSV infection can provoke the development of autoimmune conditions (antiphospholipid syndrome, autoimmune thyroiditis, autoimmune vasculitis, etc.). In addition, when HSV is integrated into the genetic apparatus of cells, neoplastic transformation of cells is possible. Thus, HSV is one of the increased risk factors for developing body and cervical cancer and other cancers. Also, HSV infection is one of the leading causes of spontaneous abortions, premature births, and the birth of children with pathologies of the central nervous system and internal organs. HPHI is associated with many “diseases of civilization” - atherosclerosis, coronary heart disease in people under 50 years of age, etc. Severe HPHI can be a marker of cancer and AIDS [7].

Depending on the number and severity of relapses, mild, moderate and severe courses of the disease are distinguished (Table 1).

In severe cases of HSV infection, the simultaneous appearance of several lesions (for example, in the genital area, lips, wings of the nose), as well as the sequential occurrence of rashes of different localization (one relapse against the background of another), the duration of the exacerbation can reach 16–20 days. At the site of the rash, patients feel heat, burning, pain, tension and/or itching of the skin. A group of bubbles filled with transparent content appears on the infiltrated skin. Bubbles can merge into a continuous multi-chamber element. Their transparent contents then become cloudy. The bubbles subsequently open, forming small erosions, or dry out and turn into crusts. A secondary bacterial infection may develop. With relapses, HSV often affects the same areas of the skin. As a rule, with severe infection, the physical and mental condition of patients worsens significantly. In some patients, during the period of relapse, weakness, fever, chills, myalgia, cephalalgia, arthralgia, irritability, sleep disturbance, emotional lability increase or appear; severe depressive states requiring drug correction may also develop. According to US health authorities, HSV infection of anogenital localization is the cause of depression and suicide in approximately 10% of cases. The severe course of the genital form of HSV infection with frequent relapses leads to disruption of the patient’s normal sexual function; the disease often creates conflict situations in the family and at work. Treatment of patients with severe HSV infection is a complex task and should include both drug therapy and psychological adaptation of the patient.

In patients with severe HSV infection, in most cases there is no persistent and significant clinical effect in response to episodic courses of combination therapy (antiviral and immunotropic drugs, restorative drugs). As a rule, such patients change many medical institutions in search of adequate help.

As the disease progresses, many adverse reactions to medications or intolerance to them appear; in some cases, HSV resistance to acyclovir, IFN-a, and other drugs develops. Immunostimulants used empirically may provide relief when taken, but in many cases they are ineffective and even worsen the clinical course of the disease. Manifestations of secondary immunodeficiency worsen, other infections occur, subdepressive states turn into persistent mental disorders, patients lose faith in recovery and in the ability of modern medicine to help them.

To develop modern approaches to the treatment and control of HSV infection and a more in-depth understanding of the pathogenesis of the disease, we studied the state of various parts of the antiviral defense and the cytokine system in patients with severe and extremely severe HSV infection of anogenital and labial localization, as well as the degree of infection ( systemicity of the disease) and the frequency of combination with other herpesvirus infections.

We examined 102 patients suffering from severe HSV infection for more than 2 years (28 men and 74 women, average age 34 ± 1.5 years) and having a relapse rate of more than six per year.

Moreover, 60 patients had from 6 to 11 relapses of HSV infection per year, and 42 patients had from 12 to 20 relapses. In most patients, anogenic or mixed localization of herpes predominated. The average duration of severe disease was 9.3 ± 1.2 years. The control group consisted of 32 practically healthy volunteers (14 men and 18 women, average age - 32 ± 1.6 years). The analysis of a number of parameters studied included the results of an examination of patients with a mild course of the disease (36 people - 10 men, 26 women, average age - 33.4 ± 2.1 years, with a relapse rate of 2.9 ± 0.8 per year). During relapses, the patients' complaints were characteristic. Depression, irritability, memory loss and other disorders of the physical and mental state and cognitive functions were common.

Many patients had a history of repeated courses of antiviral and/or immunotropic therapy, which had an ambiguous effect: either a short-term positive effect on the course of HSV infection, or worsening and development of relapse during or after the cessation of immunocorrection. Such anamnestic data reflect the severity of immune deficiency and the inadequacy of empirical therapy without assessing the immune status and individual selection of immunocorrectors, as well as restorative therapy - immunorehabilitation [5].

When examining patients with severe HSV infection, many markers of secondary immunodeficiency were identified in the form of chronic infectious and inflammatory diseases of various localizations, with a mixed nature of the microflora and, in most cases, its resistance to repeated courses of antibiotic therapy. Of 102 patients with chronic severe HSV infection, the following were identified:

• 86.3% had chronic recurrent diseases of the respiratory tract (chronic pharyngitis, chronic tracheitis, chronic laryngitis, chronic bronchitis, chronic sinusitis, repeated otitis);
• 88.2% had chronic recurrent diseases of the urogenital tract of mixed origin (cystitis, urethritis, vulvovaginitis, adnexitis, salpingoophoritis, prostatitis);
• 50–70% have astheno-vegetative and astheno-depressive syndrome, the formation of chronic fatigue syndrome;
• 91.2% had dysbiosis of the intestinal flora, chronic inflammatory diseases of the gastrointestinal tract (chronic enterocolitis, chronic gastroduodenitis);
• 25–30% have pseudo-allergic skin reactions (itching, urticaria, dermatitis).

These data indicate the need for an integrated approach to the treatment of severe HSV infection, taking into account the complications of secondary immunodeficiency.

The presence of HSV infection was confirmed based on medical history, clinical data, and the detection of HSV deoxyribonucleic acid (DNA) by polymerase chain reaction (PCR) in discharge from the rash. The study of immune status included determination of the main subpopulations of lymphocytes CD3+, CD4+, CD8+, CD72+, CD16+, activation markers of lymphocytes of the major histocompatibility complex - HLa-DR+, CD11b in peripheral blood using monoclonal antibodies. The content of immunoglobulins (Ig) a, M, G, and circulating immune complexes (CIC) in blood serum was also determined. The functional activity of neutrophils—the production of reactive oxygen species that provide bactericidal activity—was determined using the nitroblue tetrazolium test (NBT test). The stimulated NBT test was studied by incubation in vitro with a Staphylococcus aureus culture. Interferon status was assessed by the level of serum IFN and production of IFN a by leukocytes upon stimulation with New Castle disease virus and IFN ( upon stimulation with phytohemagglutinin. Quantitative content of cytokines (IFN α, IFN γ, TNF α, IL-1β, IL-2, IL-4 IL-6) in blood plasma/serum was determined by enzyme-linked immunosorbent assay (ELISA) using test systems (ProCon, St. Petersburg, and Vector-Best, Novosibirsk).

In addition, a PCR study of biological materials was carried out for the presence of DNA of HSV types 1 and 2 and other herpes group viruses: cytomegalovirus, human herpes virus (HHV) type 6, Epstein-Barr virus. The amplification programs we used made it possible to detect viral DNA at a level corresponding to their active replication. The presence of active viral replication was confirmed by semi-quantitative PCR studies and serological tests.

As a result of the study, laboratory signs of secondary immunodeficiency were found in patients with severe HSV infection.

Thus, the majority of patients (91%) did not have an adequate increase in IgG production in response to recurrent HSV infection (Fig. 1). With a recurrence rate of HSV infection of 6–11 relapses per year, a low level of IgG was detected in 25% of patients; with a frequency of 12–20 relapses per month, it was detected in 64.3% of patients. More than 70% of patients had an increased level of CEC by 1.5–2.0 times the normal level. It is known that long-term circulation of CEC can lead to their deposition on the vascular endothelium and serve as one of the factors in the formation of autoimmune pathology.

In the majority of patients with severe HSV infection (70%), disturbances were found in the system of natural and/or specific cytotoxicity (Fig. 2) - a decrease in the content of mature activated natural killer cells CD16+ (less than 11%), T-killers and/or CTLs CD8+ (less than 27%). It is important to note that a pronounced decrease in the level of CD8+ (which also includes suppressor cells) in most cases was combined with an increase in the level of CD4+ and the immunoregulatory index, which is a risk factor for the formation of autoimmune processes. As is known, natural and specific cytotoxicity systems play a leading role in antiviral defense.

In patients with severe HSV infection during relapse, the number of natural killer cells was significantly lower than normal and 2 times lower than the average for persons with mild disease. In almost half of the patients with HSV infection, the identified disorders were combined with disimmunoglobulinemia and deficiency of IgG production. The level of HLa-DR+ lymphocytes, which reflect the production of IL-2 and carry the DR+ receptor, necessary for recognizing virus-infected cells and other immune reactions, was reduced in 39% of patients with HSV infection (its increase was noted only in 17.4% of patients).

The detected disturbances in cytotoxicity systems and their activation markers during HSV infection indirectly indicate an insufficient level of production of IL-2 by T-helper type 1 cells, one of the most important links in the cytokine network, necessary for a complete antiviral immune response.

When studying the functional state of neutrophils in patients with severe HSV infection, an increase in the spontaneous NBT test was detected in almost half of the cases. However, the parameters of the stimulated NBT test and the stimulation index, on the contrary, were significantly reduced in the majority of patients, which indicates that their reserve abilities of neutrophils were depleted.

When studying the interferon status of patients during an exacerbation of HSV infection, differences were identified between mild and severe disease. Thus, the level of serum IFN in patients with mild disease was increased by 2 times compared to the control group (p < 0.05). In severe cases of infection, on the contrary, relapse was accompanied by a low level of serum IFN. The stimulated production of IFN a and IFN g was also reduced, and to a significantly greater extent precisely in cases of severe HSV infection.

Thus, the majority of patients with HSV infection showed severe deficiency of the interferonogenesis system, which correlates with data on the depletion of the reserve abilities of neutrophils in these patients.

We also studied the content of the main pro-inflammatory ILs (IL-1β, TNF α, IL-2 and a number of other ILs) in the blood serum during the period of relapse and during the period of illness outside of rashes. It turned out that in patients with severe HSV infection on days 2–3 of relapse there is no adequate response from pro-inflammatory ILs. In the majority of patients (90%), insufficiency of IL production was detected, and in approximately 10% of patients the studied ILs were not detected in the blood. It should be noted that during the non-rash period, a long-term increase in the level of one or two types of cytokines was also detected.

During a PCR examination of patients with severe HSV infection (the main group), the Epstein–Barr virus (in 76.5% of cases) and HHV type 6 (in 63.5% of cases) were most often found in the oropharyngeal area. Cytomegalovirus infection was detected in 11.0% of patients in this group (in the epithelial cells of saliva, urethra, cervical canal, and in urine sediment). In cases of mild HSV infection (comparison group), the DNA of the above viruses was detected significantly less frequently (Table 2). In general, in severe cases of the disease, the proportion of patients with HSV monoinfection was only 5%, and in mild cases it was about 72% (Table 3).

Thus, it was found that in 95.6% of patients with HSV infection with severe disease, other viruses of the herpes group actively replicate, which allows us to consider this form of the disease as a mixed viral severe infection.

Above, we noted the serious problems that arise in the treatment of HSV infection. As our studies have shown, a major role in the pathogenesis of the disease is played by secondary immunodeficiency, often combined with impaired cytokine production, as well as the presence of a mixed viral herpetic infection. In addition, against the background of these powerful interrelated factors, infectious and inflammatory diseases of the mucous membranes are added to the underlying disease. As a rule, these factors are not taken into account when treating patients with HSV infection.

Treatment of HSV infection should include suppression of viral replication during the period of exacerbation, as well as the formation of a complete immune defense in order to prevent relapses. Previously, we outlined in detail the principles of treatment for IPHI [3, 4]. To stop the exacerbation of herpes infection, acyclic nucleotides (acyclovir, valacyclovir, famciclovir) are used, the action of which is associated with the ability to disrupt the process of HSV replication at the stage of viral DNA synthesis and assembly of viral particles. The effectiveness of acyclic nucleotides depends on their bioavailability, the sensitivity of the virus to the drug, the adequacy of the dose, the duration and frequency of treatment, and the timing of the start of treatment. Prescribing these drugs from the first day of relapse (acyclovir - in a daily dose of at least 1000–1600 mg) helps to quickly stop it (Table 4).

For patients with HSV infection with frequent relapses (six or more relapses per year), in order to prevent them, suppressive administration of acyclic nucleotides is recommended for a long time, which can lead to drug remission during the treatment period. At the same time, a decrease in the frequency of relapses after cessation of treatment (compared to the period before therapy) is observed in only 20% of patients [2]. Acyclic nucleotides of the new generation - valacyclovir and famciclovir, compared to acyclovir, have higher bioavailability with the possibility of two- and three-fold administration, but these drugs are very expensive.

After a year of continuous antiviral therapy, treatment is interrupted to assess the number of relapses. For patients whose relapse rate continues to be unacceptably high, it is advisable to restart treatment [2]. With long-term or frequent therapy with acyclic nucleotides, side effects (gastrointestinal pain, dizziness, etc.) may occur; in some cases, virus resistance to this group of drugs develops. Agents that suppress HSV replication also include glycyrrhizic acid (found in licorice), IFN α (reaferon, viferon, realdiron, etc.) and inducers of its synthesis (amixin, cycloferon, ridostin, poludan, etc.). In case of severe and prolonged course of HSV infection, in the case of a course of use of these drugs during monotherapy, an insufficient clinical effect is noted; with long-term use, known side and undesirable effects develop. IFN a represents only part of the antiviral defense of the immune system and cannot replace its other parts if they fail. In addition, as mentioned above, herpes viruses are able to block the action of IFN α. As clinical experience and our data show [5, 6], the use of immunocorrectors without assessing the immune status, individual selection and control of their action is ineffective or can lead to increased immune dysfunction or hyporeactivity of a number of immune components due to inadequate stimulation. It should be emphasized that the prescription of drugs for topical use (ointments containing acyclovir, sodium foscarnet; epigen intim spray (glycyrrhizic acid), bonafton) is only auxiliary in nature, since blistering rashes on the skin are only one of the manifestations of severe HSV infection. The herpes virus, as shown in the literature and our experience, can replicate in other cells and organs (in the oropharyngeal region, lymph nodes, rectal mucosa, etc.). In addition, our research shows that severe HSV infection is, in fact, not a mono- but a mixed viral infection that develops against the background of secondary immunodeficiency, which changes the view on the examination and treatment of these patients.

We will indicate the principles of examination and treatment of patients with severe HSV infection.

Necessary examinations:

• General clinical examination - for the presence of concomitant diseases and infections (respiratory organs, gastrointestinal tract, urogenital tract - ultrasound examination, magnetic resonance therapy, etc.).
• PCR to detect HHV 4 and 6, cytomegalovirus, hepatitis viruses and intracellular infections (chlamydia, etc.).
• Complete immunological examination.
• Study of hormonal status.
• Study of tumor marker levels over time.
• Carrying out rheumatic tests in dynamics.
• If necessary, oncology search.

Treatment of exacerbation:

• Acyclic methods (acyclovir, valacyclovir, famciclovir) orally for 7–14 days.
• Locally: bonafton, acyclovir, Zovirax, Epigen, etc.
• Detoxification - according to the severity of the condition (enterosorption, plasmapheresis, hemosorption).
• Replacement complex immunotherapy (intravenous Ig, thymic peptides, IFN α and γ, IL preparations).
• Antioxidants comprehensively according to survey data.
• Metabolics.
• Vitamin therapy.
• Laser therapy.
• If necessary, treatment in a hospital.

Treatment of concomitant diseases: treatment and correction of identified concomitant disorders, diseases - chronic infections of the respiratory tract, urogenital tract and gastrointestinal tract, dysbacteriosis, hormonal dysfunctions, metabolic syndrome, depression, etc.

Relapse prevention:

• Eliminate provoking factors (occupational hazards, cold, nervous and physical overload, alcohol abuse, etc.).
• Eliminate other factors that suppress the immune system (poor diet, lack of sleep, smoking, physical inactivity, etc.).
• According to the examination, repeated courses of replacement immunotherapy, other types of immunocorrection, immunorehabilitation.
• The use of IFN, IFN inducers, glycyrrhizic acid preparations, isoprenazine (bivalent drugs with antiviral and immunotropic effects) in a course regimen.
• Prolonged courses of abnormal nucleotides.
• Antioxidants.
• Vitamin therapy, metabolism.
• Dynamic observation.

In conclusion, it must be emphasized that the heterogeneity of disturbances in the immune system during HSV infection requires a differentiated approach to their correction. It seems important to further study the cytokine response in dynamics during severe disease. It is advisable to study the effect of cytokines IL-2 (roncoleukin), IFN γ (gammaferon, ingaron) and other drugs, accompanied by individual selection of treatment regimens, on the course of the disease.

Literature

1. Khakhalin L.N. Herpes simplex viruses in humans // Consilium Medicum. 1999. T. 1. No. 1. P. 5–18.
2. European standards for the diagnosis and treatment of sexually transmitted diseases. M.: Medical literature, 2003. pp. 102–110.
3. Malashenkova I.K., Didkovsky N.A. Principles of immunocorrective therapy for secondary immunodeficiencies associated with chronic viral-bacterial infection // Russian Medical Journal. 2002. T. 10. No. 21. P. 973–977.
4. Malashenkova I.K., Didkovsky N.A., Tanasova A.N., Shchepetkova I.N., Levko A.A. Principles of therapy for herpesvirus infection // Doctor.Ru. 2004. No. 4. pp. 26–30.
5. Malashenkova I.K., Didkovsky N.A., Levko A.A. On the role of individual selection of immunocorrectors // Pharmateka. 2004. pp. 118–122.
6. Levko A. A. The importance of individual selection of immunocorrectors in the complex therapy of chronic recurrent prostatitis caused by urogenital infection: abstract. dis. ...cand. honey. Sci. M., 2005.
7. Shulzhenko A. E., Vikulov G. Kh., Tutushkina T. V. Herpetic infections - present and future // Difficult patient. 2003. No. 4. T. 1. P. 6–15.

N. A. Didkovsky , Doctor of Medical Sciences, Professor I. K. Malashenkova , Candidate of Medical Sciences Zh. Sh. Sarsaniya , Candidate of Biological Sciences A. N. Tanasova, I. N. Zuikova, I. A. Zuikov, N. M Khitrik Research Institute of Physico-Chemical Medicine, MMA named after. I. M. Sechenova, Moscow

Galavit and coronavirus/COVID-19

Galavit does not have a direct antiviral effect, that is, the drug does not directly affect the coronavirus. The mechanism of action of Galavit is realized in indirect ways: the drug makes the immune system response optimal

, avoiding excess (cytokine storm).

In the case of coronavirus infection (COVID-19), Galavit should be of great benefit, preventing the development of severe forms

any infectious disease.
Galavit gently reduces the overall inflammatory response in the body and reduces elevated body temperature, which makes the use of NSAIDs ( ibuprofen, paracetamol
, etc.) unnecessary. Thanks to the stimulation of phagocytosis, Galavit also makes it unnecessary to prescribe antibiotics for COVID-19, which still do not act on the virus and are prescribed more just in case. This leads to the emergence of antibiotic-resistant strains of bacteria.

It is best to start taking Galavit from the first day

suspected coronavirus infection, in which case COVID-19 or other respiratory infection should be mild, without high fever or complications. If the treatment was started later, at the stage of coronavirus pneumonia, then the temperature should drop and the patient should gradually recover. The more severe the patient’s condition, the more noticeable the effect of Galavit.