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Mervat A M youssef
Ebtisam Shawky hmed
Dalia Tarik Kamal
khalid Elsayh,
Mai A Abdelfatta
Hyam Hassan Mahran Mahran
Mostafa M Embaby


Bone marrow failure, SARS-CoV-2 infection, Children


Viral infections can cause direct and indirect damage to hematopoietic stem cells.

The objectives of this study were to identify the frequency and severity of aplastic anemia in Severe acute respiratory syndrome coronavirus 2 ( SARS-CoV-2) infected children as well as recognition of the response to treatment

Methodology: 13 children with newly-diagnosed severe aplastic anemia enrolled in this prospective clinical trial. Blood samples were obtained from all patients to detect SARS-CoV-2 antibodies, and nasopharyngeal swabs were collected for reverse-transcription Polymerase Chain Reaction to detect  SARS-CoV-2 viruses.  According to the laboratory results,  patients were classified in to SARS-CoV-2 positive  antibodies and SARS-CoV-2  negative antibodies .  Both groups received combined cyclosporine (CsA) + Eltrombopag (E-PAG). The hematological response either complete response (CR)or partial response (PR), no response (NR) and overall response (OR) rates of combined E-PAG + CsA treatment after 6 months were evaluated.

Results: Four children were recognized to have aplastic anemia and SARS-CoV-2 positive antibodies. Two patients fulfilled the hematological criteria for CR and no longer required transfusion of packed red blood cells (PRBCs) or platelets and  one had PR  and were still PRBC transfusion-dependent but no longer required platelet transfusion. The remaining patient showed NR and he had died before reaching the top of the  HSCT waiting list. Moreover, six patients in the SARS-CoV-2 negative antibodies group had CR while three patients had PR. The difference in ANC, Hg, and platelet counts between both groups was not significant.

Conclusion: SARS-CoV-2 virus is added to several viral infections known to be implicated in the pathogenesis of aplastic anaemia. Studies are needed to establish a definitive association and determine whether the response of bone marrow failure to standard therapy differ from that of idiopathic cases.


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1- Bacigalupo A, Hows J, Gluckman E, et al. Bone marrow transplantation (BMT) versus immunosuppression for the treatment of severe aplastic anaemia (SAA): a report of the EBMT SAA working party. Br J Haematol. 1988;70:177–182.
2- Montane E, Ibanez L, Vidal X, et al. Epidemiology of aplastic anemia: a prospective multicenter study. Haematologica. 2008;93:518–523
3- Bessler M, Mason P, Link D, et al. Inherited bone marrrow failure syndromes. In: DGN, SHO, DG, et al., editors. Nathans and Oski’s Hematology of infancy and childhood. 8. Philadelphia: W. B. Saunders Co; 2014.

4- Risitano AM, Maciejewski JP, Green S, et al. In-vivo dominant immune responses in aplastic anaemia: molecular tracking of putatively pathogenetic T-cell clones by TCR beta-CDR3 sequencing. Lancet. 2004;364:355–364.

5- Kagan WA, Ascensao JA, Pahwa RN, et al. Aplastic anemia: presence in human bone marrow of cells that suppress myelopoiesis. Proc Natl Acad Sci U S A. 1976;73:2890–2894.

6- Kordasti S, Marsh J, Al-Khan S, et al. Functional characterization of CD4+ T cells in aplastic anemia. Blood. 2012;119:2033–2043.

7- King KY, Goodell MA. Inflammatory modulation of HSCs: viewing the HSC as a foundation for the immune response. Nat Rev Immunol (2011) 11:685–92.
8- Brown KE, Young NS. Parvoviruses and bone marrow failure. Stem Cells (1996) 14:151–63.
9- Mishra B, Malhotra P, Ratho RK, Singh MP, Varma S, Varma N. Human parvovirus B19 in patients with aplastic anemia. Am J Hematol (2005) 79:166–7.
10- Morinet F, Leruez-Ville M, Pillet S, Fichelson S. Concise review: anemia caused by viruses. Stem Cells (2011) 29:1656–60.
11- Young NS, Calado RT, Scheinberg P. Current concepts in the pathophysiology and treatment of aplastic anemia. Blood (2006) 108:2509–1
12- Mirantes C, Passegué E, Pietras EM. Pro-inflammatory cytokines: emerging players regulating HSC function in normal and diseased hematopoiesis. Exp Cell Res (2014) 329:248–54
13- de Bruin AM, Voermans C, Nolte MA. Impact of interferon-γ on hematopoiesis. Blood (2015) 124:2479–87.
14- Helge D. Hartung, Timothy S. Olson, and Monica Bessler, Acquired Aplastic Anemia in Children Pediatr Clin North Am. 2013 Dec; 60(6): 1311–1336.
15- Harrison A.G., Lin T., Wang P. Mechanisms of SARS-CoV-2 transmission and pathogenesis. Trends Immunol. 2020;41(12):1100–1115.
16- D'Errico S., Zanon M., Montanaro M., Radaelli D., Sessa F., Di Mizio G., Montana A., Corrao S., Salerno M., Pomara C. More than pneumonia: distinctive features of SARS-cov-2 infection. From autopsy findings to clinical implications: a systematic review. Microorganisms. 2020;8(11)
17- Oran D.P., Topol E.J. Prevalence of asymptomatic SARS-CoV-2 infection : a narrative review. Ann. Intern. Med. 2020;173(5):362–367.
18- Kuba K, Imai Y, Rao S, Gao H, Guo F, Guan B et al (2005) A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury. Nat Med 11(8):875–879.
19- Li MY, Li L, Zhang Y, Wang XS (2020) Expression of the SARS-CoV-2 cell receptor gene ACE2 in a wide variety of human tissues. Infect Dis Poverty 9(1):45.
20- Shokrollah Elahi. Hematopoietic responses to SARS-CoV-2 infection, Cell Mol Life Sci. 202213;79(3):187.
21- Zhi ZEKZ Subspecialty Group of Hematology, Society of Pediatrics, Chinese Medical Association the editorial board, Chinese Journal. of Pediatrics. Recommendations for diagnosis and treatment of acquired aplastic anemia in children. Chin J Pediatr. 52(2):103–6(2014).
22-Camitta B, Rozman C, Marin P, Nomdedeu B, Montserrat E. Criteria for severe aplastic anaemia. Lancet.331:303–4 (1988).
23- Lesmana H, Jacobs T, Boals M, Gray N et al.(2021)Eltrombopag in children with severe aplastic anemia Pediatr Blood Cancer. 68(8):e29066.
24- Wire MB, Li X, Zhang J, Sallas W, et al. (2018), Ouatas T Modeling and simulation support eltrombopag dosing in pediatric patients with immune thrombocytopenia. Clin Pharmacol Ther 104(6):1199–207
25- Angelica Barone , Annunziata Lucarelli 2, Daniela Onofrillo et al. (2015), Marrow Failure Study Group of the Pediatric Haemato-Oncology Italian Association; Diagnosis and management of acquired aplastic anemia in childhood. Guidelines from the Marrow Failure Study Group of the Pediatric Haemato-Oncology Italian Association (AIEOP) Blood Cells Mol Dis, 55(1):40-7
26- Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX et al (2020) Clinical characteristics of coronavirus disease 2019 in China J Emerg Med. 2020 Apr; 58(4): 711–712.
27- Upchurch DM, Wong MS, Yuan AH, Haderlein TP, McClendon J, Christy A, Washington DL.COVID-19 infection in the Veterans Health Administration: gender-specific racial and ethnic differences. Womens Health Issues. 2022;32:41–50.
28-.Lee, N. C. J., Patel, B., Etra, A., Bat, T., Ibrahim, I. F., Vusirikala, M., Chen, M., Rosado, F., Jaso, J. M., Young, N. S., & Chen, W. (2022). SARS-CoV-2 infection associated with aplastic anemia and pure red cell aplasia. Blood advances, 6(13), 3840–3843.
29-Avenoso D, Marsh JCW, Potter V, et al. SARS-CoV-2 infection in aplastic anaemia. Haematologica. 2022;107(2):541-543.
30-Hock H, Kelly HR, Meyerowitz EA, Frigault MJ, Massoth LR. Case 31-2021: a 21-year-old man with sore throat, epistaxis, and oropharyngeal petechiae. N Engl J Med. 2021;385(16):1511-1520.
31- Chakravarthy R, Murphy ML, Ann Thompson M, McDaniel HL, Zarnegar-Lumley S, Borinstein SC. SARS-CoV-2 infection coincident with newly diagnosed severe aplastic anemia: a report oftwo cases. Pediatr Blood Cancer. 2022;69(4):e29433.
32 - Pascutti MF, Erkelens MN, Nolte MA. Impact of viral infections on hematopoiesis: from beneficial to detrimental effects on bone marrow output.Front Immunol. 2016;7:364.
34-Terpos E, Ntanasis-Stathopoulos I, Elalamy I, Kastritis E, Sergentanis TN, Politou M, Psaltopoulou T, Gerotziafas G, Dimopoulos MA. Hematological findings and complications of COVID-19. Am J Hematol. 2020;95(7):834–47.
35-Wang F, Hou H, Luo Y, Tang G, Wu S, Huang M, Liu W, Zhu Y, Lin Q, Mao L. The laboratory tests and host immunity of COVID-19 patients with different severity of illness. JCI insight. 2020; 5(10).
36-Ranjima M, Gobbur RH. Severe Aplastic Anemia Secondary to SARS CoV-2 Infection- A Case Report. Journal of Pediatrics, Perinatology and Child Health 5 (2021): 230-237.
37- Fatemeh Nejatifar, Ezat Hesni, Ali Akbar Samadani A Novel Case Report of Severe Aplastic Anemia with COVID Infection. Ethiop J Health Sci. 2023 Jan; 33(1): 177–181.
38- Weiskopf D, Schmitz KS, Raadsen MP, Grifoni A, Okba NM, Endeman H, van den Akker JP, Molenkamp R, Koopmans MP, van Gorp EC. Phenotype and kinetics of SARS-CoV-2–specific T cells in COVID-19 patients withacute respiratory distress syndrome. Sci Immunol. 2020;5(48):eabd2071.
39- Wang F, Hou H, Yao Y, Wu S, Huang M, Ran X, Zhou H, Liu Z, Sun Z.Systemically comparing host immunity between survived and deceased COVID-19 patients. Cell Mol Immunol. 2020;17(8):875–7.
40- Sharma C, Ganigara M, Galeotti C, Burns J, Berganza FM, Hayes DA, Singh-Grewal D, Bharath S, Sajjan S, Bayry J. Multisystem inflammatory syndrome in children and Kawasaki disease: a critical comparison. NatRev Rheumatol. 2021;17(12):731–48

41-Martinez OM, Bridges ND, Goldmuntz E, Pascual V. The immune roadmap for understanding multi-system inflammatory syndrome in children: opportunities and challenges. Nat Med. 2020;26(12):1819–24.
42- Fara A, Mitrev Z, Rosalia RA, et al. Cytokine storm and COVID-19: a chronicle of pro-inflammatory cytokines. Open Biol 10 (2020): 200160.
43- Velier M, Priet S, Appay R, et al. Severe and Irreversible Pancytopenia Associated With SARS-CoV-2 Bone Marrow Infection in a Patient With Waldenstrom Macro-globulinemia. Clinical Lymphoma Myeloma and Leukemia 21 (2021): e503-e505
44- Hernandez JM, Quarles R, Lakshmi S, et al. Pancytopenia and Profound Neutropenia as a Sequela of Severe SARS-CoV-2 Infection (COVID-19) With Concern for Bone Marrow Involvement. Open Forum Infec-tious Diseases 8 (2021).
45- Smith JN, Kanwar VS, MacNamara KC. Hematopoietic stem cell regulation by Type I and II interferons in the pathogenesis of acquired aplastic anemia. Front Immunol. 2016;7:330.