Stasiv M. COVID-19 and Multisystem Inflammatory Syndrome associated with SARS-CoV-2 in children: Clinical-immunological features of their course

Українська версія

Thesis for the degree of Doctor of Philosophy (PhD)

State registration number

0824U001886

Applicant for

Specialization

  • 228 - Педіатрія

27-05-2024

Specialized Academic Board

ДФ 35.600.103 (ID5194)

Danylo Halytsky Lviv National Medical University

Essay

This research is devoted to enhancing the diagnosis and prognosis of various severity variants of the course and development of complications in children with COVID-19 and MIS-C associated with SARS-CoV-2 based on the analysis of clinical features, biochemical, immunological, and instrumental examination data, taking into account the disease severity and age. The study involved 143 children aged 1 to 18 years, among whom 110 (76.92%) patients had COVID-19 and 33 (23.07%) had MIS-C associated with SARS-CoV-2. A moderate form of COVID-19 developed in 72.72% patients, with a median age of 8.00 years, while a severe form occurred in 27.27% patients, with a median age of 12.05 years, (p < 0.05). MIS-C associated with SARS-CoV-2 was diagnosed in 23.07% children, with a median age of 10.40 years. Patients with COVID-19 and MIS-C associated with SARS-CoV-2 were divided into three age groups: 1 to 5 years, 5 to 10 years, and 10 to 18 years. Among hospitalized children, patients aged 10 to 18 years predominated – 44.54% children with COVID-19 and 57.57% with MIS-C associated with SARS-CoV-2. The main symptoms upon hospitalization were: elevated body temperature (95.5%), general weakness (91.8%), and decreased appetite (80.0%). Additionally, dry cough (50.0%), headache (22.7%), sore throat (19.1%), and malaise (6.4%) were reported. Dyspnea troubled all patients with severe COVID-19: mixed type in 21 (70.0%) cases and expiratory in nine (30.0%) cases. Watery diarrhea occurring 1 to 3 times and abdominal pain were statistically significant in patients aged 10 to 18 years (p < 0.05). During the investigation of inflammation markers, it was found that the level of CRP was higher in the group of patients with severe COVID-19 compared to moderate cases (p < 0.05). Correlation analysis revealed a weak association between CRP level and disease severity (r = +0.29; p < 0.05). A direct correlation was established between the severity of COVID-19 and the level of procalcitonin (r = +0.51; p < 0.05). The study also showed that the albumin level determined on the third day of hospitalization decreased with increasing procalcitonin (r = -1.00; p < 0.0001). The study results indicate a higher level of IL-6 and IL-10 in patients with severe COVID-19 compared to those with moderate disease (p < 0.05). The IL-2 level was negative in all studied groups (p > 0.05). Patients with severe COVID-19 had statistically significantly higher levels of D-dimer compared to children with moderate disease: 791.00 ng FEU/mL [540.00; 1844.50] versus 368.00 ng FEU/mL [149.25; 921.25], respectively (p < 0.05), which was confirmed by a direct correlation (r = +0.35; p < 0.05). The results of IgA analysis to SARS-CoV-2 indicate its appearance from the second week of illness in patients with severe COVID-19 (p < 0.05), suggesting the potential importance of this marker in disease prognosis. It was observed that early appearance and prolonged presence of IgG-N and IgG-S to SARS-CoV-2 in the blood were observed in all patients. The mean value of IgG-S was higher from the second week of the study, with its highest level observed during the period from 31 to 90 days. Compared to IgG-S, the level of IgG-N was significantly lower. The severity of the disease correlated with IgG-S (from 8 to 14 days) (r = +0.303; p < 0.05). In patients with MIS-C, hyperthermia prevailed, detected in 81.8% of cases. In patients in the age group of 10 to 18 years, a statistically significant increase in the frequency of watery diarrhea and abdominal pain was observed compared to other age groups (p < 0.05). A maculo-papular rash was found in the majority of children - 78.8%, while hemorrhagic rash was present in 57.6% of cases. Edema syndrome was diagnosed in 42.4% patients Mucous membrane involvement was observed in the majority of patients - 81.1%. It should be noted that patients with MIS-C exhibited an increase in leukocyte count upon hospitalization, with a subsequent rise in this parameter on the third day of hospitalization. Marked neutrophilia was observed in all patients both at the time of admission and on the third day of treatment. In children aged 5 to 10 years, the platelet count upon admission was the lowest with a median value of 102.00 × 109/L [89.75; 111.50] (p < 0.05). The study revealed that upon hospitalization and on the third day of treatment, children with MIS-C exhibited a significant increase in levels of CRP and procalcitonin. Additionally, elevated levels of IL-6 and IL-10 were observed upon admission – 12.65 pg/mL [9.45; 18.88], and 25.88 pg/mL ± 63.50, respectively. When studying the proteinogram in patients with MIS-C presenting with edema syndrome and ascites on the third day of treatment, a nearly twofold decrease in albumin was observed – 35.00 g/L [23.50; 39.70]. The study results demonstrated a significant increase in D-dimer levels in all MIS-C patients upon admission, particularly in children aged 10 to 18 years.

Research papers

1. Lytvyn H, Stasiv M, Basa N, Kulachkovska I, Cisarὸ F, Pellicano R. Multisystem inflammatory syndrome in children associated with SARS-CoV-2 infection and severe abdominal syndrome: the Lviv “OHMATDYT” (Western Ukraine) experience. Minerva Pediatrics [Internet]. 2022;74(5):600-608. DOI: 10.23736/S2724-5276.22.06785-4 Available from: https://www.minervamedica.it/en/journals/minerva-pediatrics/article.php?cod=R15Y2022N05A0600

2. Stasiv M, Mishchuk V, Basa N, Lytvyn H. Successful use of ECMO in the treatment of acute respiratory distress syndrome associated with SARS-CoV-2 in two pediatric cases. Germs [Internet]. 2022;12(2):308-315. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9719379/pdf/germs-12-02-308.pdf DOI: 10.18683/germs.2022.1334

3. Lytvyn HO, Stasiv MV, Mishchuk VR, Avramenko IY. COVID-19 challenge, in which a three-year-old girl won. Wiadomości Lekarskie. 2021;74(10):2530-2534. Available from: https://wiadlek.pl/wp-content/uploads/archive/2021/WLek2021101.pdf DOI: 10.36740/WLek202110130

4. Troyanovska O, Dorosh O, Lytvyn H, Tsymbalyuk I, Vorobel O,…, Stasiv M, et al. Characteristics of COVID-19 in pediatric patients with hematological malignancies. Acta Haematologica Polonica [Internet]. 2022;53(4):273-276. Available from: https://journals.viamedica.pl/acta_haematologica_polonica/article/view/AHP.a2022.0035/68780 DOI: 10.5603/AHP.a2022.0035

I.Y. Avramenko, N.S. Kosmynina, M.V. Stasiv VRM. COVID-19 in Children: Multisystem Inflammatory Syndrome. Ukr J Perinatol Pediatr. 2022;90(2):24–30. Available from: https://med-expert.com.ua/journals/wp-content/uploads/2022/08/06.pdf DOI: 10.15574/PP.2022.90.17

6. Литвин ГО, Личковська ОЛ, Стасів МВ, Міщук ВР. Боротьба за життя дитини з COVID-19 тривалістю 68 днів. Інфекційні хвороби. 2021;4:58-63. DOI: 10.11603/1681-2727.2021.4.12840 Доступно: https://ojs.tdmu.edu.ua/index.php/inf-patol/article/view/12840

7. Литвин ГО, Стасів МВ. Пaндемія COVID-19 тривалістю у два роки: проблемні питання педіатрії та шляхи їх вирішення. Інфекційні хвороби. 2022;2:58-72. Доступно: https://ojs.tdmu.edu.ua/index.php/inf-patol/article/view/13190/12324 DOI: 10.11603/1681-2727.2022.2.13190

8. Литвин ГО, Покровська ТВ, Дибас ІВ, Стасів МВ. Особливості перебігу інфекційних хвороб у дітей, переміщених із зон бойових дій. Інфекційні хвороби. 2022;2:73-81. Доступно: https://ojs.tdmu.edu.ua/index.php/inf-patol/article/view/13192/12325 DOI: 10.11603/1681-2727.2022.2.13192

9. Стасів МВ. Кінетика IgM, IgA, IgG до SARS-CoV-2 у дітей з COVID-19 Львівської області в різні періоди інфекційного процесу залежно від тяжкості перебігу та віку. Acta Medica Leopoliensia. 2023;29((3-4)):41–57. Доступно: https://amljournal.com/index.php/journal/article/view/361/238 DOI: 10.25040/aml2023.3-4.041

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