<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE root>
<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:ali="http://www.niso.org/schemas/ali/1.0/" article-type="research-article" dtd-version="1.2" xml:lang="en"><front><journal-meta><journal-id journal-id-type="publisher-id">Kazan medical journal</journal-id><journal-title-group><journal-title xml:lang="en">Kazan medical journal</journal-title><trans-title-group xml:lang="ru"><trans-title>Казанский медицинский журнал</trans-title></trans-title-group></journal-title-group><issn publication-format="print">0368-4814</issn><issn publication-format="electronic">2587-9359</issn><publisher><publisher-name xml:lang="en">Eco-Vector</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">568720</article-id><article-id pub-id-type="doi">10.17816/KMJ568720</article-id><article-categories><subj-group subj-group-type="toc-heading" xml:lang="en"><subject>Theoretical and clinical medicine</subject></subj-group><subj-group subj-group-type="toc-heading" xml:lang="ru"><subject>Теоретическая и клиническая медицина</subject></subj-group><subj-group subj-group-type="article-type"><subject>Research Article</subject></subj-group></article-categories><title-group><article-title xml:lang="en">Serotonin and 5-hydroxyindoleacetic acid are involved in the pathogenesis of COVID-19 in children</article-title><trans-title-group xml:lang="ru"><trans-title>Серотонин и 5-гидроксииндолуксусная кислота вовлечены в патогенез COVID-19 у детей</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-4686-1231</contrib-id><name-alternatives><name xml:lang="en"><surname>Nigmatullina</surname><given-names>Razina R.</given-names></name><name xml:lang="ru"><surname>Нигматуллина</surname><given-names>Разина Рамазановна</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>D. Sci. (Biol.), Prof., Depart. of Physiology</p></bio><bio xml:lang="ru"><p>докт. биол. наук, проф., каф. нормальной физиологии</p></bio><email>razinar@mail.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-6662-3548</contrib-id><name-alternatives><name xml:lang="en"><surname>Sadykova</surname><given-names>Dinara I.</given-names></name><name xml:lang="ru"><surname>Садыкова</surname><given-names>Динара Ильгизаровна</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>M.D., D. Sci. (Med.), Prof., Head of the Depart., Depart. of Hospital Pediatrics</p></bio><bio xml:lang="ru"><p>докт. мед. наук, проф., зав. каф., каф. госпитальной педиатрии</p></bio><email>sadykovadi@mail.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-5722-8490</contrib-id><name-alternatives><name xml:lang="en"><surname>Makarova</surname><given-names>Tamara P.</given-names></name><name xml:lang="ru"><surname>Макарова</surname><given-names>Тамара Петровна</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>M.D., D. Sci. (Med.), Prof., Depart. of Hospital Pediatrics</p></bio><bio xml:lang="ru"><p>докт. мед. наук, проф., каф. госпитальной педиатрии</p></bio><email>makarova-kgmu@mail.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-3676-2130</contrib-id><name-alternatives><name xml:lang="en"><surname>Khusnutdinova</surname><given-names>Liliya R.</given-names></name><name xml:lang="ru"><surname>Хуснутдинова</surname><given-names>Лилия Ринатовна</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>PhD Stud., Depart. of Hospital Pediatrics</p></bio><bio xml:lang="ru"><p>асп., каф. госпитальной педиатрии</p></bio><email>husnutdinova-lil@mail.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-1732-7443</contrib-id><name-alternatives><name xml:lang="en"><surname>Slastnikova</surname><given-names>Eugeniya S.</given-names></name><name xml:lang="ru"><surname>Сластникова</surname><given-names>Евгения Сергеевна</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>M.D., Cand. Sci. (Med.), Assistant, Depart. of Hospital Pediatric; Pediatrician</p></bio><bio xml:lang="ru"><p>канд. мед. наук, асс., каф. госпитальной педиатрии; врач — детский кардиолог, липидолог</p></bio><email>e.slastnikova@mail.ru</email><xref ref-type="aff" rid="aff1"/><xref ref-type="aff" rid="aff2"/></contrib></contrib-group><aff-alternatives id="aff1"><aff><institution xml:lang="en">Kazan State Medical University</institution></aff><aff><institution xml:lang="ru">Казанский государственный медицинский университет</institution></aff></aff-alternatives><aff-alternatives id="aff2"><aff><institution xml:lang="en">Children's Republican Clinical Hospital,</institution></aff><aff><institution xml:lang="ru">Детская республиканская клиническая больница</institution></aff></aff-alternatives><pub-date date-type="pub" iso-8601-date="2023-12-05" publication-format="electronic"><day>05</day><month>12</month><year>2023</year></pub-date><volume>104</volume><issue>6</issue><issue-title xml:lang="en"/><issue-title xml:lang="ru"/><fpage>843</fpage><lpage>850</lpage><history><date date-type="received" iso-8601-date="2023-08-23"><day>23</day><month>08</month><year>2023</year></date><date date-type="accepted" iso-8601-date="2023-11-20"><day>20</day><month>11</month><year>2023</year></date></history><permissions><copyright-statement xml:lang="en">Copyright ©; 2023, Eco-Vector</copyright-statement><copyright-statement xml:lang="ru">Copyright ©; 2023, Эко-Вектор</copyright-statement><copyright-year>2023</copyright-year><copyright-holder xml:lang="en">Eco-Vector</copyright-holder><copyright-holder xml:lang="ru">Эко-Вектор</copyright-holder><ali:free_to_read xmlns:ali="http://www.niso.org/schemas/ali/1.0/" start_date="2026-12-05"/></permissions><self-uri xlink:href="https://kazanmedjournal.ru/kazanmedj/article/view/568720">https://kazanmedjournal.ru/kazanmedj/article/view/568720</self-uri><abstract xml:lang="en"><p><bold>Background.</bold> The new coronavirus infection COVID-19 is a pressing health problem around the world. This disease affects the respiratory, cardiovascular and other systems. The role of serotonin as one of the key factors in COVID-19 is discussed in the literature.</p> <p><bold>Aim.</bold> Determination of the concentration of serotonin and its metabolite 5-hydroxyindoleacetic acid in the blood serum of children in the acute period of COVID-19 for use as a diagnostic criterion for the severity of the disease.</p> <p><bold>Material and methods.</bold> A study that included 141 children aged 0 to 17 years was conducted: 92 patients hospitalized in a hospital with a diagnosis of COVID-19 without concomitant pathology made up the study group, 49 healthy children were included in the control group. The subjects were divided into two age groups: younger (0–2 years) and older (3–17 years). The groups of patients and children from the control group were comparable in age and gender. A study of the concentration of serotonin and its metabolite — 5-hydroxyindoleacetic acid — in the blood was carried out using high-performance liquid chromatography, and the results of laboratory and instrumental research methods (obtained from medical records) were evaluated. Based on the results of computed tomography, the proportion of involvement of the lung parenchyma in the pathological process was calculated: CT0 — absence of lung damage; CT1 — less than 25%; CT2 — 25–49%; CT3 — 50–74%; CT4 — more than 75%. Quantitative data were described using median (Me) and lower and upper quartiles (Q1–Q3). To analyze the data, the Pearson χ2 test, nonparametric Kruskal–Wallis and Mann–Whitney tests, as well as the ROC curve method were used. A correlation analysis was carried out using the Spearman coefficient and an assessment of the dependence of a quantitative variable on factors using the linear regression method.</p> <p><bold>Results.</bold> In children with COVID-19 aged 0–2 years, the concentration of serotonin (969.41 pmol/ml) in the blood serum was statistically significantly higher by 49.1 times, in the group of 3–17 years (637.87 pmol/ml) — by 24.5 times compared to age-matched controls (19.74 pmol/ml; p &lt;0.001 and 26.0 pmol/ml; p &lt;0.001, respectively). The concentration of 5-hydroxyindoleacetic acid in patients 0–2 years old (204.90 pmol/ml) was 4.7 times higher relative to healthy children (43.56 pmol/ml; p=0.003), and in the older age group (78.25 pmol/ml) — 2.4 times higher (32.65 pmol/ml; p=0.012), which suggests increased breakdown of serotonin under the influence of monoamine oxidase A. Maximum concentrations of serotonin in blood serum were detected in children aged 0–2 years (1808.79 pmol/ml) with damage to the lung parenchyma from 50 to 74% (grade 3 according to computed tomography). However, in children aged 3–17 years, the maximum concentrations of serotonin (2036.95 pmol/ml) were detected with lung damage ranging from 25 to 49% (grade 2 according to computed tomography). In patients with COVID-19, when the concentration of serotonin in the blood was above 1046.5 pmol/ml, grade 2–4 lung lesions were predicted according to computed tomography, sensitivity 62.5%, specificity 75%.</p> <p><bold>Conclusion.</bold> With COVID-19, a significant increase in the concentration of serotonin and 5-hydroxyindoleacetic acid in the blood was detected in children.</p></abstract><trans-abstract xml:lang="ru"><p><bold>Актуальность.</bold> Новая коронавирусная инфекция COVID-19 — актуальная проблема здравоохранения всего мира. Это заболевание поражает дыхательную, сердечно-сосудистую и другие системы. В литературе обсуждают роль серотонина как одного из ключевых факторов при COVID-19.</p> <p><bold>Цель.</bold> Определение концентрации серотонина и его метаболита 5-гидроксииндолуксусной кислоты в сыворотке крови детей в остром периоде COVID-19 для использования как диагностического критерия тяжести заболевания.</p> <p><bold>Материал и методы исследования.</bold> Проведено исследование, включающее 141 ребёнка в возрасте от 0 до 17 лет: 92 пациента, госпитализированных в стационар с диагнозом COVID-19 без сопутствующей патологии, составили исследуемую группу, 49 здоровых детей вошли в контрольную группу. Исследуемые были разделены на две возрастные группы: младшую (0–2 лет) и старшую (3–17 лет). Группы больных и детей из контрольной группы были сопоставимы по возрасту и полу. Проведено исследование концентрации серотонина и его метаболита — 5-гидроксииндолуксусной кислоты — в крови методом высокоэффективной жидкостной хроматографии, оценены результаты лабораторных и инструментальных методов исследования (получены из историй болезни). По результатам проведения компьютерной томографии был произведён подсчёт доли вовлечения в патологический процесс паренхимы лёгких: КТ0 — отсутствие поражения лёгких; КТ1 — менее 25%; КТ2 — 25–49%; КТ3 — 50–74%; КТ4 — более 75%. Количественные данные описаны с помощью медианы (Me) и нижнего и верхнего квартилей (Q1–Q3). Для анализа данных использованы критерий χ2 Пирсона, непараметрические критерии Краскела–Уоллиса и Манна–Уитни, а также метод ROC-кривых. Проведены корреляционный анализ при помощи коэффициента Спирмена и оценка зависимости количественной переменной от факторов методом линейной регрессии.</p> <p><bold>Результаты.</bold> У детей с COVID-19 в возрасте 0–2 лет концентрация серотонина (969,41 пмоль/мл) в сыворотке крови статистически значимо выше в 49,1 раза, в группе 3–17 лет (637,87 пмоль/мл) — в 24,5 раза по сравнению с одновозрастным контролем (19,74 пмоль/мл; р &lt;0,001 и 26,0 пмоль/мл; р &lt;0,001 соответственно). Концентрация 5-гидроксииндолуксусной кислоты у пациентов 0–2 лет (204,90 пмоль/мл) была в 4,7 раза выше относительно здоровых детей (43,56 пмоль/мл; p=0,003), а в старшей возрастной группе (78,25 пмоль/мл) — в 2,4 раза выше (32,65 пмоль/мл; р=0,012), что предполагает усиленный распад серотонина под действием моноаминоксидазы А. Максимальные концентрации серотонина в сыворотке крови выявлены у детей в возрасте 0–2 лет (1808,79 пмоль/мл) при поражении паренхимы лёгких от 50 до 74% (3-я степень по данным компьютерной томографии). Однако у детей в возрасте 3–17 лет максимальные концентрации серотонина (2036,95 пмоль/мл) выявлены при поражении лёгких от 25 до 49% (2-я степень по данным компьютерной томографии). У пациентов с СOVID-19 при концентрации серотонина в крови выше 1046,5 пмоль/мл прогнозируются поражения лёгких 2–4-й степени по данным компьютерной томографии, чувствительность 62,5%, специфичность 75%.</p> <p><bold>Вывод.</bold> При COVID-19 у детей выявлено значительное повышение концентрации серотонина и 5-гидроксииндолуксусной кислоты в крови.</p></trans-abstract><kwd-group xml:lang="en"><kwd>serotonin</kwd><kwd>5-HT</kwd><kwd>5-hydroxyindoleacetic acid</kwd><kwd>5-HIAA</kwd><kwd>children</kwd><kwd>COVID-19</kwd></kwd-group><kwd-group xml:lang="ru"><kwd>серотонин</kwd><kwd>5-НТ</kwd><kwd>5-гидроксииндолуксусная кислота</kwd><kwd>5-ГИУК</kwd><kwd>дети</kwd><kwd>COVID-19</kwd></kwd-group><funding-group><award-group><funding-source><institution-wrap><institution xml:lang="ru">Исследование выполнено за счёт гранта Российского научного фонда</institution></institution-wrap></funding-source><award-id>№ 23-15-00417, https://rscf.ru/project/23-15-00417/</award-id></award-group></funding-group></article-meta></front><body></body><back><ref-list><ref id="B1"><label>1.</label><mixed-citation>Zhao YH, Zhao L, Yang XC, Wang P. Cardiovascular complications of SARS-CoV-2 infection (COVID-19): A systematic review and meta-analysis. Rev Cardiovasc Med. 2021;22(1):159–165. DOI: 10.31083/j.rcm.2021.01.238.</mixed-citation></ref><ref id="B2"><label>2.</label><mixed-citation>Akhmetova MZ, Tykezhanova GМ, Mindubaeva FА, Nigmatullina RR. Serotonin: Biological properties and its receptors. Bulletin Of The Karaganda University. Biology. Medicine. Geography Series. 2019;(2):71–79.</mixed-citation></ref><ref id="B3"><label>3.</label><mixed-citation>Rieder M, Gauchel N, Bode C, Duerschmied D. Serotonin: A platelet hormone modulating cardiovascular disease. J Thromb Thrombolysis. 2021;52(1):42–47. DOI: 10.1007/s11239-020-02331-0.</mixed-citation></ref><ref id="B4"><label>4.</label><mixed-citation>Aflyatumova GN, Nigmatullina RR, Sadykova DI, Chibireva MD, Fugetto F, Serra R. Endothelin-1, nitric oxide, serotonin and high blood pressure in male adolescents. Vasc Health Risk Manag. 2018;14:213–223. DOI: 10.2147/VHRM.S170317.</mixed-citation></ref><ref id="B5"><label>5.</label><mixed-citation>Tarbit E, Singh I, Peart JN, Bivol S, Rose'Meyer RB. Increased release of serotonin from rat primary isolated adult cardiac myofibroblasts. Sci Rep. 2021;11(1):20376. DOI: 10.1038/s41598-021-99632-y.-</mixed-citation></ref><ref id="B6"><label>6.</label><mixed-citation>Zaid Y, Puhm F, Allaeys I, Naya A, Oudghiri M, Khalki L, Limami Y, Zaid N, Sadki K, Ben El Haj R, Mahir W, Belayachi L, Belefquih B, Benouda A, Cheikh A, Langlois MA, Cherrah Y, Flamand L, Guessous F, Boilard E. Platelets can associate with SARS-Cov-2 RNA and are hyperactivated in COVID-19. Circ Res. 2020;127(11):1404–1418. DOI: 10.1161/CIRCRESAHA.120.317703.</mixed-citation></ref><ref id="B7"><label>7.</label><mixed-citation>Zaid Y, Guessous F, Puhm F, Elhamdani W, Chentoufi L, Morris AC, Cheikh A, Jalali F, Boilard E, Flamand L. Platelet reactivity to thrombin differs between patients with COVID-19 and those with ARDS unrelated to COVID-19. Blood Adv. 2021;5(3):635–639. DOI: 10.1182/bloodadvances.2020003513.</mixed-citation></ref><ref id="B8"><label>8.</label><mixed-citation>Ha S, Jin B, Clemmensen B, Park P, Mahboob S, Gladwill V, Lovely FM, Gottfried-Blackmore A, Habtezion A, Verma S, Ro S. Serotonin is elevated in COVID-19-associated diarrhoea. Gut. 2021;70(10):2015–2017. DOI: 10.1136/gutjnl-2020-323542.</mixed-citation></ref><ref id="B9"><label>9.</label><mixed-citation>Kanova M, Kohout P. Serotonin — its synthesis and roles in the healthy and the critically ill. Int J Mol Sci. 2021;22(9):4837. DOI: 10.3390/ijms22094837.</mixed-citation></ref><ref id="B10"><label>10.</label><citation-alternatives><mixed-citation xml:lang="en">Temporary guidelines. Prevention, diagnosis and treatment of new coronavirus infection (COVID-19). Version 9 (26.10.2020). https://static0.minzdrav.gov.ru/system/attachments/attaches/000/052/548/original/%D0%9C%D0%A0_COVID-19_%28v.9%29.pdf (access date: 13.08.2023). (In Russ.)</mixed-citation><mixed-citation xml:lang="ru">Временные методические рекомендации "Профилактика, диагностика и лечение новой коронавирусной инфекции (COVID-19)", версия 9 (26.10.2020). https://static0.minzdrav.gov.ru/system/attachments/attaches/000/052/548/original/%D0%9C%D0%A0_COVID-19_%28v.9%29.pdf (дата обращения: 13.08.2023).</mixed-citation></citation-alternatives></ref><ref id="B11"><label>11.</label><mixed-citation>Diorio C, McNerney KO, Lambert M, Paessler M, Anderson EM, Henrickson SE, Chase J, Liebling EJ, Burudpakdee C, Lee JH, Balamuth FB, Blatz AM, Chiotos K, Fitzgerald JC, Giglia TM, Gollomp K, Odom John AR, Jasen C, Leng T, Petrosa W, Vella LA, Witmer C, Sullivan KE, Laskin BL, Hensley SE, Bassiri H, Behrens EM, Teachey DT. Evidence of thrombotic microangiopathy in children with SARS-CoV-2 across the spectrum of clinical presentations. Blood Adv. 2020;4(23):6051–6063. DOI: 10.1182/bloodadvances.2020003471.</mixed-citation></ref><ref id="B12"><label>12.</label><mixed-citation>Watts SW, Davis RP. 5-Hydroxtryptamine receptors in systemic hypertension: An arterial focus. Cardiovasc Ther. 2011;29(1):54–67. DOI: 10.1111/j.1755-5922.2010.00173.x.</mixed-citation></ref><ref id="B13"><label>13.</label><citation-alternatives><mixed-citation xml:lang="en">Sadykova DI, Nigmatullina RR, Aflyatumova GN. The role of serotonergic system in cardiovascular diseases development in children. Kazan Medical Journal. 2015;96(4):665–669. (In Russ.) DOI: 10.17750/KMJ2015-665.</mixed-citation><mixed-citation xml:lang="ru">Садыкова Д.И., Нигматуллина Р.Р., Афлятумова Г.Н. Роль серотонинергической системы в развитии заболеваний сердца и сосудов у детей. Казанский медицинский журнал. 2015;96(4):665–669. DOI: 10.17750/KMJ2015-665.</mixed-citation></citation-alternatives></ref><ref id="B14"><label>14.</label><citation-alternatives><mixed-citation xml:lang="en">Sveshnikov DS, Kuchuk AV, Smirnov VM, Cherepanova GV. Serotonergic mechanisms of regulation of the systemic circulation vessels lumen. Kazan Medical Journal. 2016;97(1):89–94. (In Russ.) DOI: 10.17750/KMJ2016-89.</mixed-citation><mixed-citation xml:lang="ru">Свешников Д.С., Кучук А.В., Смирнов В.М., Черепанова Г.В. Серотонинергические механизмы регуляции просвета сосудов большого круга кровообращения. Казанский медицинский журнал. 2016;97(1):89–94. DOI: 10.17750/KMJ2016-89.</mixed-citation></citation-alternatives></ref><ref id="B15"><label>15.</label><mixed-citation>Monassier L, Maroteaux L. Serotonin and cardiovascular diseases. In: Serotonin: The mediator that spans evolution. Pilowsky PM, editor. Amsterdam: Elsevier, 2019. p. 203–238. DOI: 10.1016/b978-0-12-800050-2.00012-7.</mixed-citation></ref></ref-list></back></article>
