COVID-19 Lessons from Wuhan: Frequently Asked Questions
(Version 1.0; last updated April 1, 2020)
Input from Drs. Di Yang, Weiming Li, Mei Hong
Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Wuhan, China
What impact has SARS-CoV-2 had on treatment of hematology patients in your institution in Wuhan, China?
Based on observation and investigation of patients with serious hematologic diseases, particularly malignancies, we found that the patients infected by SARS-CoV-2 during chemotherapy had atypical symptoms and more complications. SARS-CoV-2 showed extremely fast and widespread transmission among patients on our hematology ward, with a very high mortality (>50%) for inpatients with both SARS-CoV-2 and a hematologic malignancy at our center.
We know that SARS-CoV-2 infection results in both innate immune effects and late development of adaptive specific immunity. Monocytes, NK cells and other immune cells secrete cytokines to kill virus-infected cells but can also result in a serious cytokine storm in some patients. Specific immune response against the virus is the key to eventual clearance. Hematologic malignancy patients undergoing chemotherapy who acquire SARS-CoV-2 will likely have defects in both innate and adaptive immunity, likely contributing to the very high mortality we have observed in these patients.
What suggestions can you give about delaying or changing initial treatment for various hematologic disorders based on your experience in Wuhan?
The outbreak severely restricted the number of beds available for non-SARS-CoV-2 medical care and required converting ward rooms from single to double or triple occupancy. In addition, visits to the hospital increase the risk of infection. Thus, we classified patients with malignant hematological diseases into 2 categories. For patients with stable or chronic disease, we deferred therapies and imposed a watch and wait strategy. For patients in need of urgent treatment, we substituted oral chemotherapy or targeted agents whenever possible, for instance giving older patients with AML venetoclax 100mg qd, d1-14 and d14-28, for each 4 week cycle. This reduces the need for blood transfusions and inpatient admissions.
What about transplantation?
We deferred all transplants for non-emergent situations at our hospital in Wuhan. If the patient had to receive an emergent transplant, we first excluded SARS-CoV-2 in the patient. We placed the patient in an aseptic laminar flow room filtering 99.9% of particles with diameter greater than 0.3μm through a high efficiency filter. While SARS-CoV-2 is about 0.1μm, it appears to be primarily transmitted by particles such as droplets or dust with a size >0.3μm. Therefore, we believe use of laminar flow can block the transmission of most coronavirus particles. However, small particles with virus may get through, and thus the area needs standard disinfection treatments. In addition, laminar flow wards are in a positive pressure state with air flowing from the inside to the outside. Once the patient is infected, it will increase the risk of virus transmission, therefore if any patient becomes infected, laminar flow must be suspended1.
Are you adjusting treatment of aplastic anemia?
In patients with aplastic anemia, if there is no evidence of co-infection with SARS-CoV-2, the focus should be on protecting these patients from the risk of infection. There is no need to adjust immunosuppressive drugs such as cyclosporine (CsA). A fall in blood counts due to dropping the dosage could reduce immunity and increasing the need for transfusions. For patients diagnosed as having SARS-CoV-2, we do consider lowering the dosage of immunosuppressive drugs such as CsA temporarily. Although there are reports indicating that CsA can block MERS-CoV-induced replication and cytotoxicity2,3, the highest concentrations of plasma CsA achieved in vivo are much lower than EC50 of MERS—CoV in vitro. However, if CsA is stopped completely, blood counts may drop, so we have been making moderate CsA dose reductions.
What about patients with CML?
According to our experience in Wuhan, CML patients with SARS-CoV-2 do not need to have TKIs stopped or dose-adjusted. However, we must pay attention to the interaction between SARS-CoV-2 therapeutics and TKIs. Meanwhile, the efficacy and adverse effects of TKIs should be monitored routinely, and clinicians can adjust TKI dose or switch between TKIs as needed based on drug interactions4.
References
- Hong M, Fang Y, Xia LH. Prevention and control of COVID-19 infection in a department of hematology. Chinese Journal of Hematology. 2020.41 DOI:10.3760/cma.j.issn.0253-2727.2020.0005
- de Wilde AH, Zevenhoven-Dobbe JC, van der Meer Y, Thiel V, Narayanan K, Makino S, Snijder EJ, van Hemert MJ. Cyclosporine A inhibits the replication of diverse coronaviruses. J Gen Virol. 2011, 92:2542-2548.
- de Wilde AH, Raj VS, Oudshoorn D et al. MERS-coronavirus replication induces severe in vitro cytopathology and is strongly inhibited by cyclosporin A or interferon-alpha treatment. J Gen Virol, 2013. 94: 1749-1760.
- Wang DY, Guo JM, Yang ZZ et al. The first report of the prevalence of COVID-19 in chronic myelogenous leukemia patients in the core epidemic area of China: multicenter cross sectional survey. https://www.medrxiv.org/content/10.1101/2020.03.12.20034876v2 [published online ahead of print Mar 12, 2020]. DOI:10.1101/2020.03.12.20034876
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