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Главная / Архив / 2023 год / MEDICUS № 1 (49), January / INTERNATIONAL RECOMMENDATIONS «POST-COVID SYNDROME». WHAT'S NEW?

INTERNATIONAL RECOMMENDATIONS «POST-COVID SYNDROME». WHAT'S NEW?

Дата публикации: 23.01.2023

UDC 616.98:578.834.1-036.1

 

INTERNATIONAL RECOMMENDATIONS

«POST-COVID SYNDROME». WHAT'S NEW?

 

D.А. Kapsultanova, Candidate of Medical Sciences,

Associate Professor of the Department of Internal Diseases

Kazakh National Medical University named after S.D. Asfendiyarov

(050000, Kazakhstan. Almaty, st. Tole Bi, 94)

Email: aktolkyn_te@mail.ru

 

Sh.B. Zhangelova, Candidate of Medical Sciences,

Associate Professor, Professor of the Department

Kazakh National Medical University named after S.D. Asfendiyarov

(050000, Kazakhstan. Almaty, st. Tole Bi, 94)

Email: aktolkyn_te@mail.ru

 

G.Е. Gappar, 2nd year Resident

Kazakh National Medical University named after S.D. Asfendiyarov

(050000, Kazakhstan. Almaty, st. Tole Bi, 94)

Email: aktolkyn_te@mail.ru

 

М.М. Tauyekel, 2nd year Resident

Kazakh National Medical University named after S.D. Asfendiyarov

(050000, Kazakhstan. Almaty, st. Tole Bi, 94)

Email: aktolkyn_te@mail.ru

 

А.E. Tursynaly, 2nd year Resident

Kazakh National Medical University named after S.D. Asfendiyarov

(050000, Kazakhstan. Almaty, st. Tole Bi, 94)

Email: aktolkyn_te@mail.ru

 

Abstract. The article considered the pathophysiological mechanisms of development and treatment of post-COVID syndrome according to international recommendations.

Keywords: COVID-19; post-covid syndrome.

 

The new coronavirus infection COVID-19, which has been shaking the world for more than a year, is a serious public health problem. This infection can occur with long-term, varied and severe symptoms that are little studied and are of great interest to doctors of various specialties. This disease is poorly studied as it affects COVID-19 survivors at all levels of disease severity, even younger adults, children, and those who not hospitalized.

According to some authors, a complete “recovery” after an infection occurred in about 20 million people [4]. At the same time, other specialists, in particular clinicians, approve that the symptoms of the disease can persist for a long time, be of varying severity and lead to serious consequences, up to a significant change in the structure and function of organs [5, 8]. So Greenhalgh Trisha, et al. (2020) were the first who give the concept of "long-covid", which meant the presence of symptoms after an infection for more than 3 weeks from the onset of the first symptoms or subacute COVID-19 and more than 12 weeks – chronic COVID-19 [5]. Thus, we can speak about “post-COVID syndrome” when a patient develops symptoms or their combination within 12 weeks after recovery from COVID-19 and their presence cannot be explained by the presence of other diseases [8]. While the exact definition of long COVID may be absent, the most common symptoms reported in many studies are fatigue and dyspnoea that last for months after acute COVID-19 [12].

“Post-covid syndrome” can develop not only after a coronavirus infection, but also in some vaccinated patients, which is possibly associated with the activation of monocytes by the spike protein of the vaccine [8]. Almost 70-80 % of patients who have been ill are in a painful condition and complain about a decrease in the quality of their life and the presence of various symptoms, often affecting cognitive functions [8, 12].

There are several theories explaining the cause of the development of post-COVID syndrome, they do not contradict, but rather complement each other. Each of them is based on the theory of direct damage by the virus to the vascular endothelium and, as a result, tissues, organs and almost all body systems [1, 12].

In the Protocol of the International Alliance FLCCC “Long Haul COVID-19 Syndrom” (Treatment of long-term COVID-19 syndrome-2021), experts also put forward theories that may explain the presence of various clinical forms of “post-covid syndrome” [13].

Thus, the long-term persistence of the virus and the preservation of its residues in monocytes and some types of (CD4+) lymphocytes leads to their activation and a permanent immune response, as the immune system tries to eliminate the foreign protein and viral RNA fragments [7].

Mast cell activation syndrome (MCAC) also develops, which are located in large numbers in the brain in the region of the median eminence of the hypothalamus in the perivascular space. Given the high neurotropism of the coronavirus, there is an indirect stimulation of mast cells by corticotropin-releasing hormone with the release of pro-inflammatory mediators of histamine, chemokines, tryptases, and cytokines. They can cause inflammation of the components of the neurovascular unit and the appearance of an appropriate clinical picture [11].

Neurological symptoms in post-COVID syndrome can also be associated with the expression of the microcirculatory part of the cerebral vessels of ACE-2 receptors by SARS CoV-2 pseudovirions, inflammation, endothelial dysfunction, and thrombus formation [10].

With regard to the issue of long-term respiratory symptoms, it is possible that they may be due to unresolved organizing pneumonia associated with the activation of pulmonary macrophages.

An analysis of many studies on the management of patients who have had a coronavirus infection has shown that the clinical manifestations of the “post-covid syndrome” are diverse and can occur with varying degrees of severity [3]. The defeat of the respiratory system manifests itself in the form of shortness of breath, persistent cough, stagnation in the lungs; – cardiovascular – palpitations, cardialgia, rhythm disturbance, uncontrolled blood pressure, hypotension;

  • nervous system – severe weakness, headaches, depression, insomnia, dizziness, loss of smell, phantom odors;
  • musculoskeletal system – pain in muscles and joints, inability to perform normal daily activities (PA).
  • gastrointestinal tract – anorexia, diarrhea, vomiting, nausea, etc.;
  • skin manifestations, such as itching, rash, dermographism, etc.

The distribution of symptoms of "post-covid syndrome" into groups is necessary for individual organ-specific therapy [13]. Considering that there are no large-scale clinical trials and generally accepted treatment of "post-COVID syndrome", current recommendations for the management of such patients are based on the pathophysiological mechanisms of COVID-19 and post-COVID diseases. Taking into account the studies of our Russian colleagues, it should be noted that it is undesirable to use negative medical technologies – those methods that have no evidence of effectiveness, are not pathogenetically justified and can cause harm that exceeds or is comparable to the benefits received. Negative technologies for post-COVID syndrome include:

    • application of minerals: zinc, magnesium;
    • use of vitamins: vitamin D, vitamin C, all B vitamins, including vitamin B12, folic acid, (vitamin B9), without absolute indications;
    • methylene blue;
    • use of physical activity methods (walking, running, cycling and other exercise methods);
    • use of baths and saunas;
    • use of ultraviolet irradiation (including local) and insolation. Often contribute to the development of exacerbations! [14].

A wide range of symptoms that may occur in patients with post-COVID syndrome, it is currently serious health problem worldwide. Correct assessment will help determine the clinical etiology and build a treatment plan. To date, the drug ivermectin, included in the Protocol of the International Alliance FLCCC "Long Haul COVID-19 Syndrom" (2021), is proposed as the initial stage in the treatment of "post-COVID syndrome". But data on the use of ivermectin for the treatment of patients with "post-COVID" is still insufficient and this does not allow us to draw an unambiguous conclusion regarding this drug and include it in the treatment protocols in many countries. If therapy with ivermectin is ineffective and/or has not been prescribed and the patient is expected to have mast cell activation, then it is advisable to prescribe glucocorticosteroids and type I and II antihistamines, as well as mast cell stabilizers [6].

All patients with post-COVID syndrome should be recommended monocyte/macrophage repolarization therapy in the form of vitamin C and D, atorvastatin, omega-3 fatty acids, and melatonin. Drugs such as the tranquilizer diazepam and serotonin reuptake inhibitors are proposed in the International Protocol as second-line drugs that affect the stabilization of mast cells, and the antidepressant fluvoxamine for poor concentration, forgetfulness, and mood disorders [6].

An interesting fact is that so far the “post-covid syndrome” cannot be predicted and its appearance does not always correlate with the severity of the course of an acute coronavirus infection. Often the syndrome occurs after a mild or moderate coronavirus infection and in patients who did not need respiratory support or intensive care [13].

All the treatments provided in this article have a place to be, considering the fact there are no general protocols and randomized clinical trials, there is no evidence-based database of methods, due to the fact that very little time has passed after the surge of COVID 19. All data require confirmation and evidence.

Thus, it is not yet known which patients will develop a "post-COVID" syndrome, what will be the severity of its course, the dominant clinical symptoms and the duration of their manifestation. But one thing is clear that the basis of the organ-specific therapy of the "post-covid syndrome" requires the use of pathogenetic anti-inflammatory therapy, as well as therapy using drugs that affect the repolarization of macrophages and monocytes, the stabilization of mast cells: glucocorticosteroids, statins, omega-3 fatty acids, antihistamines, etc. [9]. Last years omega-3 were added to the COVID-19 management protocol as a recommended supplement after recovering from an illness. Recently, an American study came out that revealed the presence of omega-3 in coronavirus: people with high levels of omega-3 fatty acids in the blood had a 75 % lower risk of death than those with a deficiency of omega-3 in the blood. The results of the study are published in the journal Prostaglandins, Leukotrienes and Essential Fatty Acids. “While this pilot study does not meet the standard thresholds of statistical significance, it, together with a wealth of evidence for the anti-inflammatory effects of EPA and DHA fatty acids, strongly suggests that available marine fatty acids may reduce the risk of adverse outcomes in COVID-19. Obviously, to confirm larger studies are needed from these preliminary results," lead study author Arash Asher, MD, Samuel Oshin Comprehensive Cancer Institute at Cedars-Sinai Medical Center in Los Angeles, said in a FARI press release [2].

The use of anticoagulant drugs with pleiotropic, endothelium-stabilizing effects is also considered in the treatment of "post-covid syndrome" and is under active study.

 

REFERENCES

  1. Afrin, L., Weinstock L., Molderings G. Covid-19 hyperinflammation and post-Covid- 19 illness may be rooted in mast cell activation syndrome. Int J Infect Dis. 2020; 100:327-332. Available at: https://doi.org/10.1016/j.ijid.2020.09.016.
  2. Blood omega-3 fatty acids and death from COVID-19: A pilot study Arash Asher Nathan L. Tintle Michael Myers Laura Lockshon Heribert Bacareza William S. Harris Published:January 20, 2021DOI:https://doi.org/10.1016/j.plefa.2021.102250
  3. Carfi, A., Bernabei R., Landi F. et al. COVID-19 Post-Acute Care Study Group. Persistent symptoms in patients after acute COVID-19. JAMA.2020;324(6):603-605. doi:10.1001/jama.2020. 12603.
  4. Carlos, del Rio, Lauren F. Collins, Preeti Malani. Long-term Health Consequences of COVID -19. JAMA. 2020; 324 (17): 1723-1724. doi: 10.1001/jama.2020.19719.
  5. Greenhalgh, Trisha, Knight Matthew, A’CourtChristine, et al. Management of post-acute covid-19 in primary care. BMJ. 2020; 370: m3026.
  6. Long Haul COVID-19 Syndrom. (2021). flccc.net/flccc-protocols-a-guide-to-the-management-of-covid-19
  7. Lu, Y, Li X, Geng D et al. Cerebral micro-structutal changes in COVID-19 patients – An MRI- based 3-month follow-up study. EClinicalMedicine 2020.
  8. National, Guidance for post-COVID syndrome assessment clinics, 2020. Available at: https://www.england.nhs.uk/coronavirus/ publication/ national- guidance-for-post- covid -syndromeassessment- clinics/ (date of the application: 14.01.2021).
  9. Riche, F. Protracted immune disorders at one year after ICU discharge in patients with septic shock. Crit Care 2018; 22:42.
  10. Sirous, R, Taghvaei R, Hellinger JC et al. COVID-19-associated encephalopathy with ful- minant cerebral vasoconstriction: CT and MRI findings. Radiology Case Reports 2020; 15:2208-12.
  11. Theoharides, TT, Cholevas C, Polyzoidis K et al. Long-COVID syndrome-associated brain fog and chemofog: Luteolin to the rescue. Biofactors 2021; 47:232-41.
  12. Yong, S.J. Long COVID or post-COVID-19 syndrome: putative pathophysiology, risk factors, and treatments. Infect Dis (Lond). 2021;53(10):737–754. Available at: https://doi.org/10.1080/23744235.2021.1924397.
  13. Yong, SJ. Long-haul COVID-19: Putative pathophysiology, risk factors, and treatments. me- dRxiv 2020.
  14. Ким, М.С., Пономарева Е.Ю. ФГБОУ ВО «Саратовский ГМУ им. В.И. Разумовского» МЗ России Кафедра госпитальной терапии лечебного факультета (зав. кафедрой профессор А.П. Ребров) V международный медицинский форум Донбасса «Наука побеждать…болезнь». – Донецк, 11-12 ноября, 2021.

 

REFERENCES

  1. Afrin L., Weinstock L., Molderings G. Covid-19 hyperinflammation and post-Covid- 19 illness may be rooted in mast cell activation syndrome. Int J Infect Dis. 2020; 100:327-332. Available at: https://doi.org/10.1016/j.ijid.2020.09.016. (In English).
  2. Blood omega-3 fatty acids and death from COVID-19: A pilot study Arash Asher Nathan L. Tintle Michael Myers Laura Lockshon Heribert Bacareza William S. Harris Published:January 20, 2021DOI:https://doi.org/10.1016/j.plefa.2021.102250 (In English).
  3. Carfi A., Bernabei R., Landi F. COVID-19 Post-Acute Care Study Group. Persistent symptoms in patients after acute COVID-19. JAMA.2020;324(6):603-605. doi:10.1001/jama.2020. 12603 (In English).
  4. Carlos del Rio, Lauren F. Collins, Preeti Malani. Long-term Health Consequences of COVID -19. JAMA. 2020; 324 (17): 1723-1724. doi: 10.1001/jama.2020.19719. (In English).
  5. Greenhalgh Trisha, Knight Matthew, A’CourtChristine, Management of post-acute covid-19 in primary care. BMJ. 2020; 370: m3026. (In English).
  6. Long Haul COVID-19 Syndrom. (2021). flccc.net/flccc-protocols-a-guide-to-the-management-of-covid-19 (In English).
  7. Lu Y, Li X, Geng D. Cerebral micro-structutal changes in COVID-19 patients – An MRI- based 3-month follow-up study. EClinicalMedicine 2020 (In English).
  8. National Guidance for post-COVID syndrome assessment clinics, 2020. Available at: https://www.england.nhs.uk/coronavirus/ publication/ national- guidance-for-post- covid -syndromeassessment- clinics/ (date of the application: 14.01.2021) (In English).
  9. Riche F. Protracted immune disorders at one year after ICU discharge in patients with septic shock. Crit Care 2018; 22:42 (In English).
  10. Sirous R, Taghvaei R, Hellinger JC. COVID-19-associated encephalopathy with ful- minant cerebral vasoconstriction: CT and MRI findings. Radiology Case Reports 2020; 15:2208-2212 (In English).
  11. Theoharides TT, Cholevas C, Polyzoidis K. Long-COVID syndrome-associated brain fog and chemofog: Luteolin to the rescue. Biofactors 2021; 47:232-241 (In English).
  12. Yong S.J. Long COVID or post-COVID-19 syndrome: putative pathophysiology, risk factors, and treatments. Infect Dis (Lond). 2021;53(10):737-754. Available at: https://doi.org/10.1080/23744235.2021.1924397. (In English).
  13. Yong SJ. Long-haul COVID-19: Putative pathophysiology, risk factors, and treatments. me- dRxiv 2020 (In English).
  14. Kim M.S., Ponomareva Ye.Yu. FGBOU VO «Saratovskiy GMU im. V.I. Razumovskogo» MZ Rossii Kafedra gospital'noy terapii lechebnogo fakul'teta (zav. kafedroy professor A.P. Rebrov) V mezhdunarodnyy meditsinskiy forum Donbassa «Nauka pobezhdat'…bolezn'». – Donetsk, 11-12 noyabrya [Saratov State Medical University named after V.I. Razumovsky of the Ministry of Health of Russia Department of Hospital Therapy of the Faculty of Medicine (Head of the Department Professor A.P. Rebrov) V International Medical Forum of Donbass "Science to win... disease". – Donetsk, November 11-12 [. 2021 (In Russ.).

 

Материал поступил в редакцию 12.01.23

 

 

МЕЖДУНАРОДНЫЕ РЕКОМЕНДАЦИИ

ПО «ПОСТКОВИДНОМУ СИНДРОМУ». ЧТО НОВОГО?

 

Д.А. Капсултанова, кандидат медицинских наук, доцент кафедры внутренних болезней

Казахский национальный медицинский университет им.С.Д. Асфендиярова

(050000, Казахстан, Алматы, ул. Толе Би, 94)

Email: aktolkyn_te@mail.ru

 

Ш.Б. Жангелова, кандидат медицинских наук, доцент, профессор кафедры

Казахский национальный медицинский университет им.С.Д. Асфендиярова

(050000, Казахстан, Алматы, ул. Толе Би, 94)

Email: aktolkyn_te@mail.ru

 

Г.Е. Гаппар, резидент 2-го курса

Казахский национальный медицинский университет им.С.Д. Асфендиярова

(050000, Казахстан, Алматы, ул. Толе Би, 94)

Email: aktolkyn_te@mail.ru

 

М.М. Тауекел, резидент 2-го курса

Казахский национальный медицинский университет им.С.Д. Асфендиярова

(050000, Казахстан, Алматы, ул. Толе Би, 94)

Email: aktolkyn_te@mail.ru

 

А.Е. Турсыналы, резидент 2-го курса

Казахский национальный медицинский университет им.С.Д. Асфендиярова

(050000, Казахстан, Алматы, ул. Толе Би, 94)

Email: aktolkyn_te@mail.ru

 

Аннотация. В статье рассмотрены патофизиологические механизмы развития и лечение постковидного синдрома в свете международных рекомендации.

Ключевые слова: COVID-19; постковидный синдром.