Page 201 - 2022_02-Haematologica-web

Letters to the Editor
count, hemoglobin concentration and platelet count at three different time-points (pre-infection, at infection, and post-infection) in the four groups of the study popu- lation: newly diagnosed, on active immunosuppressive therapy, off immunosuppressive therapy and after hematopoietic stem cell transplantation.
For those patients affected by transfusion-independent non-severe AA (10/23), there was a new requirement of transfusion support in seven patients, but no cases of transition to severe/very severe AA were recorded.
Despite profound neutropenia and being on immuno- suppressive therapy, only 13% of patients (3/23) devel- oped COVID-19. This may reflect some specific, favor- able host factors (such as young age) or might be second- ary to protective immune dysregulation known to be present in AA.10 Indeed, hypotheses on the role of hyper- inflammation resulting in a more severe disease pheno- type have resulted in proposals of trials to investigate the use of agents blocking these pathways for the treatment of severe SARS-CoV-2 infection in non-AA patients.11
Despite the lack of cytokine studies or viral polymerase chain reaction analysis of bone marrow aspirates in our study, it is reasonable to speculate a potential myelosup- pressive effect of SARS-CoV-2: as demonstrated in Figure 1, patients had a clear decline in hematopoiesis, causing worsening of blood parameters and relapse of AA. However, the study does not clarify whether the virus has a direct cytotoxic effect on hematopoietic stem cells or acts through the cytokine storm or aberrant immune dysregulation following the infection and might have a bias due to non-reporting of milder cases.
We demonstrate that SARS-CoV-2 infection is another factor that can jeopardize residual hematopoiesis during AA, as previously described for other viral infections (e.g., hepatitis). The kinetics of the deterioration in blood counts after SARS-CoV-2 infection mirrors the previously reported kinetics of AA diagnosis or relapse in pregnancy. Although a clear correlation between pregnancy and the onset or relapse of AA has never been demonstrated, sev- eral groups have described worsening of hematologic indices at the onset of pregnancy and subsequent recov- ery in the post-partum period.12,13
Our study does not enable clear conclusions to be drawn about the severity and long-term prognosis of SARS-CoV-2 infection in AA; despite the lack of COVID- 19 deaths, the viral infection was a risk factor for the onset of AA and for worsening of blood parameters in patients already with AA.
This is the first report describing the outcome of AA following SARS-CoV-2 infection, and while it is encour- aging to note that most patients (including transplanted cases) made a full recovery without the development of significant symptoms, this population needs to be consid- ered at risk of complications of worsening cytopenias fol- lowing COVID-19. Indeed, one patient died as a conse- quence of infectious complications due to relapsed AA.
A possible temporal relationship between SARS-CoV2 infection and AA can be suggested in three cases in our series. Are these cases a casual association of SARS-CoV- 2 infection and AA or are they cases of secondary AA as a result of the viral insult? The detection of three new cases of AA within a total of 4.5 million cases of SARS- CoV-2 infection in the UK is intriguing. Further studies that include measurement of cytokines and other factors such as regulatory T-cell subsets are needed to character- ize the immune and inflammatory environment follow- ing SARS-CoV-2 infections in AA patients to help predict outcomes and prognosis. Furthermore, considering the availability of vaccines against SARS-CoV2 infection, it is
important to prevent cytopathic effects of the virus with a successful AA vaccination program, although close monitoring is required as vaccination-induced AA has been reported in the literature.
Daniele Avenoso,1 Judith C.W. Marsh,1 Victoria Potter,1 Antonio Pagliuca,1 Simon Slade,1 Fiona Dignan,2 Eleni Tholouli,2 Sajjan Mittal,3 Bernard Davis,4 Sudhir Tauro,5 Rachel Kesse-Adu,6 Morag Griffin,7 Elspeth Payne,8 Shreyans Gandhi1 and Austin G. Kulasekararaj1
1King’s College Hospital NHS Foundation Trust, London; 2Royal Manchester Infirmary, Manchester; 3Northampton General Hospital, Northampton; 4Whittington Hospital, London; 5University of Dundee, Dundee; 6Guys and St Thomas Hospital NHS Foundation Trust, London; 7St James University Hospitals, Leeds and 8University College London, London, UK
Correspondence:
DANIELE AVENOSO - d.avenoso@nhs.net doi:10.3324/haematol.2021.279928 Received: September 2, 2021.
Accepted: October 13, 2021.
Pre-published: October 21, 2021. Disclosures: no conflicts of interest to disclose.
Contributions: all the authors were involved in the care of the patients and contributed equally to writing this manuscript; DA col- lected and analyzed the data; AK supervised the study.
Acknowledgments: the authors thank all NHS staff for fighting the COVID-19 pandemic
References
1. Zhu N, Zhang D, Wang W, et al. A novel coronavirus from patients with pneumonia in China, 2019 N Engl J Med. 2020;382(8):727-733. 2. Yang X, Yu Y, Xu J, et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single- centered, retrospective, observational study. Lancet Respir Med.
2020;8(5):475-481.
3. Shah V, Ko Ko T, Zuckerman M, et al. Poor outcome and prolonged
persistence of SARS-CoV-2 RNA in COVID-19 patients with haematological malignancies; King’s College Hospital experience. Br J Haematol. 2020;190(5):e279-e282.
4.Dewaele K, Claeys R. Hemophagocytic lymphohistiocytosis in SARS-CoV-2 infection. Blood. 2020;135(25):2323.
5. Hersby DS, Do TH, Gang AO, Nielsen TH. COVID-19-associated pancytopenia can be self-limiting and does not necessarily warrant bone marrow biopsy for the purposes of SARS-CoV-2 diagnostics. Ann Oncol. 2021;32(1):121-123.
6. Young NS. Aplastic anemia. N Engl J Med. 2018;379(17):1643-1656. 7. Paton C, Mathews L, Groarke EM, et al. COVID-19 infection in patients with severe aplastic anaemia. Br J Haematol.
2021;193(5):902-905.
8. Camitta BM, Storb R, Thomas ED. Aplastic anemia: pathogenesis,
diagnosis, treatment, and prognosis. N Engl J Med.
1982;306(11):645-652.
9. Corman VM, Landt O, Kaiser M, et al. Detection of 2019 novel
coronavirus (2019-nCoV) by real-time RT-PCR. Eurosurveillance.
2020;25(3):2000045.
10. Dufour C, Ferretti E, Bagnasco F, et al. Changes in cytokine profile
pre- and post-immunosuppression in acquired aplastic anemia.
Haematologica. 2009;94(12):1743-1747.
11. Biran N, Ip A, Ahn J, et al. Tocilizumab among patients with
COVID-19 in the intensive care unit: a multicentre observational
study. Lancet Rheumatol. 2020;2(10):e603-e612.
12. Aitchison RGM, Marsh JCW, Hows JM, Russell NH, Gordon-Smith
EC. Pregnancy associated aplastic anaemia: a report of five cases and
review of current management. Br J Haematol. 1989;73(4):541-545. 13. Oosterkamp HM, Brand A, Kluin-Nelemans JC, Vandenbroucke JR. Pregnancy and severe aplastic anaemia: causal relation or coinci-
dence? Br J Haematol. 1998;103(2):315-316.
haematologica | 2022; 107(2)
543