Modern Pediatrics. Ukraine. (2022). 8(128): 98-104. doi 10.15574/SP.2022.128.98
Hariyan T. V. ¹, Tomashivska T. V.², Dyvonyak O. M.², Pavlyshyn G. A.¹, Boyarchuk O. R.^1
1I. Horbachevsky Ternopil National Medical University, Ukraine
²Ternopil City Children’s Hospital, Ukraine

For citation: Hariyan TV, Tomashivska TV, Dyvonyak OM, Pavlyshyn GA, Boyarchuk OR. (2022). Course of COVID-19 in immunocompromised patients. Modern Pediatrics. Ukraine. 8(128): 98–104. doi 10.15574/SP.2022.128.98.
Article received: Oct 09, 2022. Accepted for publication: Dec 20, 2022.

Purpose – to analyze the currently described variants of the course of COVID-19 in immunocompromised patients in order to inform the medical community and focus on this problem.
Two clinical cases of different course of COVID-19 in patients with primary immunodeficiencies, both mild, asymptomatic and severe, with a fatal outcome, are presented. In the first case, in a child with Nijmegen  breakage syndrome, despite lymphopenia, the course of SARS-CoV-2 was asymptomatic, which may be due to the regular administration of immunoglobulin for replacement purposes.
The peculiarity of the second case was a repeated episode of COVID-19 in an immunocompromised child with APECED. The first episode of COVID-19 in September 2020 had a mild course, but led to the manifestation of immunodeficiency symptoms. The present symptoms (retinopathy, hepatitis), except for mild mucosal candidiasis, are not part of the triad of classic APECED symptoms, although along with the reaction to the live vaccine, they made it possible to suspect immunodeficiency. Immunosuppressive therapy contributed to stabilization of hepatitis, but ocular symptoms were without positive dynamics. The second episode of COVID-19 was observed in January 2022. It proceeded with prolonged fever for 2 weeks, which was resistant to treatment, with progressive cytopenia, hypoproteinemia, hypoalbuminemia, signs of active hepatitis, hyperferritinemia, elevated triglycerides; coagulopathy with low fibrinogen levels. Subsequently, signs of pneumonia were added, confirmed by radiology. Another feature of this case was the presence of a mixed infection – COVID-19 and Epstein-Barr virus infection. The cause of death in this case was not only COVID-19 pneumonia, but also progressive macrophage activation syndrome.
Conclusions. Thus, the sequence of COVID-19 in patients with inborn errors of immunity can be either asymptomatic and mild or fatal, depending on the type of immune disorders, the therapy received, and concomitant conditions. SARS-CoV-2 in immunocompromised individuals requires close attention for timely diagnosis of life-threatening conditions.
The research was carried out in accordance with the principles of the Helsinki Declaration. The informed consent of the patient was obtained for conducting the studies.
No conflict of interests was declared by the authors.
Keywords: COVID-19, inborn errors of immunity, children.
REFERENCES
1. Bastard P, Gervais A, Le Voyer T et al. (2021). Autoantibodies neutralizing type I IFNs are present in ~4% of uninfected individuals over 70 years old and account for ~20% of COVID-19 deaths. Sci Immunol. 6 (62): eabl4340.

2. Bastard P, Orlova E, Sozaeva L et al. (2021). Preexisting autoantibodies to type I IFNs underlie critical COVID-19 pneumonia in patients with APS-1. J Exp Med 5; 18 (7): e20210554. https://doi.org/10.1084/jem.20210554; PMid:33890986 PMCid:PMC8077172

3. Belsky JA, Tullius BP, Lamb MG, Sayegh R, Stanek JR, Auletta JJ. (2021). COVID-19 in immunocompromised patients: A systematic review of cancer, hematopoietic cell and solid organ transplant patients. J Infect. 82 (3): 329-338. https://doi.org/10.1016/j.jinf.2021.01.022; PMid:33549624 PMCid:PMC7859698

4. Bode SF, Ammann S, Al-Herz W et al. (2015). The syndrome of hemophagocytic lymphohistiocytosis in primary immunodeficiencies: implications for differential diagnosis and pathogenesis. Haematologica. 100 (7): 978-988. https://doi.org/10.3324/haematol.2014.121608; PMid:26022711 PMCid:PMC4486233

5. Boyarchuk O, Kinash M, Hariyan T, Bakalyuk T. (2019). Evaluation of knowledge about primary immunodeficiencies among postgraduate medical students. Archives of the Balkan Medical Union. 54 (1): 11-19. https://doi.org/10.31688/ABMU.2019.54.1.18

6. Boyarchuk O, Predyk L, Yuryk I. (2021). COVID-19 in patients with juvenile idiopathic arthritis: frequency and severity. Reumatologia. 59 (3): 197-199. https://doi.org/10.5114/reum.2021.107590; PMid:34538947 PMCid:PMC8436806

7. Boyarchuk O, Volyanska L, Kosovska T, Lewandowicz-Uszynska A, Kinash M. (2018). Awareness of primary immunodeficiency diseases among medical students. Georgian Med News. 12 (285): 124-130.

8. Boyarchuk O, Yarema N, Kravets V et al. (2022). Newborn screening for severe combined immunodeficiency: The results of the first pilot TREC and KREC study in Ukraine with involving of 10,350 neonates. Front Immunol. 13: 999664. https://doi.org/10.3389/fimmu.2022.999664; PMid:36189201 PMCid:PMC9521488

9. Boyarchuk O. (2018). Allergic manifestations of primary immunodeficiency diseases and its treatment approaches. Asian Journal of Pharmaceutical and Clinical Research. 11 (11): 83-90.
https://doi.org/10.22159/ajpcr.2018.v11i11.29059

10. Esenboga S, Ocak M, Akarsu A et al. (2021). COVID-19 in Patients with Primary Immunodeficiency. J Clin Immunol. 41 (7): 1515-1522. https://doi.org/10.1007/s10875-021-01065-9; PMid:34231093 PMCid:PMC8260154

11. Ferré EMN, Schmitt MM, Ochoa S et al. (2021). SARS-CoV-2 Spike Protein-Directed Monoclonal Antibodies May Ameliorate COVID-19 Complications in APECED Patients. Front Immunol. 12: 720205. https://doi.org/10.3389/fimmu.2021.720205; PMid:34504497 PMCid:PMC8421855

12. GOV.UK. (2022). Guidance COVID-19: guidance for people whose immune system means they are at higher risk. URL: https://www.gov.uk/government/publications/covid-19-guidance-for-people-whose-immune-system-means-they-are-at-higher-risk/covid-19-guidance-for-people-whose-immune-system-means-they-are-at-higher-risk.

13. Henter JI, Horne A, Aricó M et al. (2007). HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 48 (2): 124-131. https://doi.org/10.1002/pbc.21039; PMid:16937360

14. Kisand K, Link M, Wolff AS et al. (2008). Interferon autoantibodies associated with AIRE deficiency decrease the expression of IFN-stimulated genes. Blood. 112 (7): 2657-2666. https://doi.org/10.1182/blood-2008-03-144634; PMid:18606876 PMCid:PMC2577576

15. Kuczborska K, Buda P, Książyk J. (2022). Long-COVID in immunocompromised children. Eur J Pediatr. 181 (9): 3501-3509. https://doi.org/10.1007/s00431-022-04561-1; PMid:35834042 PMCid:PMC9281224

16. McGonagle D, Ramanan AV, Bridgewood C. (2021). Immune cartography of macrophage activation syndrome in the COVID-19 era. Nat Rev Rheumatol. 17 (3): 145-157. https://doi.org/10.1038/s41584-020-00571-1; PMid:33547426 PMCid:PMC7863615

17. Meyts I, Bucciol G, Quinti I et al. (2021). Coronavirus disease 2019 in patients with inborn errors of immunity: An international study. J Allergy Clin Immunol. 147 (2): 520-531. https://doi.org/10.1016/j.jaci.2020.09.010; PMid:32980424 PMCid:PMC7832563

18. Ravelli A, Minoia F, Davì S, et al. (2016). 2016 classification criteria for macrophage activation syndrome complicating systemic juvenile idiopathic arthritis: a European League Against Rheumatism/American College of Rheumatology/Paediatric Rheumatology International Trials Organisation collaborative initiative. Arthritis Rheumatol. 68: 566-576.

19. Shadrin OG, Marushko TL, Volokha AP, Marushko RV. (2022). Primary immunodeficiency: IPEX-syndrome. Literature review and clinical case. Modern Pediatrics. Ukraine. 2 (122): 63-71. https://doi.org/10.15574/SP.2022.122.63

20. Yarema NM, Makukh HV, Virstyuk LM, Fedynska OV, Boyarchuk OR. (2022). A clinical case of combined immunodeficiency diagnosed by TREC assay. Modern Pediatrics. Ukraine. 5 (125): 123-127. https://doi.org/10.15574/SP.2022.125.123