Steroid Treatment in Hematologic Ptients with COVID-19: Experience of 2 cases

A 69 years old man with a positive COVID-19 PCR test, was admitted to our department on April 4, 2020. Current medical history revealed active Chronic Lymphoid Leukemia (CLL) that was treated with Ibrutinib. The patient also suffered from Obstructive Sleep Apnea (OSA), nephrolithiasis and obesity (BMI 33) (Table 1). He was admitted for persistent fever (38.3oC) and dry cough, which started 12 days prior to his hospitalization (March 23, 2020). During his pre-hospitalization period he was treated with a 5-days course of oral Levofl oxacin, as prescribed by his family physician. Following this treatment the patient had no clinical improvement, and positive COVID-19 PCR test was detected and he was admitted to our ward.

The patient was exposed to a verifi ed positive COVID-19 subject on March 18, 2020 and 4 days later he was tested and found positive for COVID-19 PCR. On admission the patient had fatigue, dry cough and mild dyspnea. He ruled out diarrhea, chills or chest pain. Physical examination revealed normal body temperature of 37.6°C, heart rate 64 beats/minute, respiratory rate 19 breaths/minute and 96% O 2 saturation measured in room air ( Figure 3). Blood pressure measurement was 121/60 mmHg. Chest x-ray on arrival showed bilateral increased interstitial markings, with no consolidation or pleural effusion ( Figure 4). On arrival the patient was categorized as a moderate disease patient.
On the third day of admission the patient's condition deteriorated: he complains of fatigue, dry cough and dyspnea, respiratory rate was 35 /min and O 2 saturation decreased to 90% in air room and no response to supplemental oxygen. Laboratory tests showed severe thrombocytopenia of 66 K/ micl and increased infl ammatory markers D-dimer 1528 ng/ mL and CRP levels 2.6 mg/dL. The patient was categorized as moderate to severe stage and intubation was considered at this stage. As a last conservative treatment at that time, we started parenteral Solu Medrol 500 mg/d and supplemental oxygen, in addition to Levofl oxacin 500mg treatment. Following the high dose corticosteroid treatment, there was a remarkable clinical improvement after 48 hours; he reported milder dry cough and no dyspnea, on examination: respiratory rate was 25 and oxygen saturation 94% in room air, laboratory tests improved: decreased serum D-dimer levels (1301 ng/mL) and ferritin levels. He no longer needed supplemental oxygen treatment. Few days later the patient was categorized as mild disease and on April 4, 2020 the patient was discharged home following two consecutive negative COVID-19 PCR tests. 2 weeks later on follow up Corona clinic he reported of weakness but no respiratory consequences.

Discussion
Effective therapies for hospitalized patients with Corona virus are steel in progress and most treatments were based on clinical trials and case reports. Steroid treatment mainly low dose dexamethasone in critical patients is only now established in met analysis that evaluated the role of corticosteroids in the management of COVID-19 patients, has shown that corticosteroids can be used in patients with critical illness with moderate to severe ARDS without the risk of increased mortality [1,2]. unit, mechanical ventilation requirement and higher mortality rate [3]. Hemato-oncological patients were reported to have mortality rate up to 40% [4]. Yet, the data on hematologic patients in the aspect of COVID-19 was at that time and still today currently limited. Hasharon hospital reopened as the fi rst and solely COVID-19 hospital in Israel, and 52 patients were admitted to our ward, Corona B ward [5]. Two of these patients had coexisting oncologic hematologic background.
Based on A recent study from the hematologic department in    Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) eruptions, patients were benefi ted from corticosteroids treatment, which helped in decreasing the infl ammatory damage [7]. These immunosuppressant agents were used to overcome the cytokine storm response from an overreaction of the immune system (8). The release of cytokines  as TNF, IL-1, IL-2, IL-6, IFN, IFN, IFN, and MCP-1, provoke free radicals secretion which are the main reason for ARDS and systemic organ failure [9].
Studies reported that high dose steroids were not benefi cial for severe lung injury treatment [10]. A retrospective study estimated the outcomes of adjuvant corticosteroid treatment on the prognosis of 244 critically ill COVID-19 patients and found that increased corticosteroid dosage was signifi cantly associated with elevated mortality risk [11]. Nevertheless, using a low-to-moderate dosage of corticosteroids, for a short period has shown to be effective for critically ill COVID-19 patients [12][13][14].

Conclusion
In this study we described the clinical course of two hematologic patients that admitted to our Corona B ward in Hasharon hospital, the fi rst COVID-19 hospital in Israel.
Although data on corticosteroids as a treatment for COVID-19 patients was controversial at that time, we decided to give it as a last resort before intubation, when the available treatments protocols failed to improve their disease course. This decision was based on the known literature regarding the effi cacy of corticosteroids treatment in the SARS and MERS eruptions. As