Patients with severe COVID-19 have a hyperinflammatory immune response
suggestive of macrophage activation. Bruton tyrosine kinase (BTK) regulates
macrophage signaling and activation. Acalabrutinib, a selective BTK inhibitor, was
administered off-label to 19 patients hospitalized with severe COVID-19 (11 on
supplemental oxygen; 8 on mechanical ventilation), 18 of whom had increasing
oxygen requirements at baseline. Over a 10-14 day treatment course, acalabrutinib
improved oxygenation in a majority of patients, often within 1-3 days, and had no
discernable toxicity. Measures of inflammation ? C-reactive protein and IL-6 ?
normalized quickly in most patients, as did lymphopenia, in correlation with
improved oxygenation. At the end of acalabrutinib treatment, 8/11 (72.7%) patients
in the supplemental oxygen cohort had been discharged on room air, and 4/8 (50%)
patients in the mechanical ventilation cohort had been successfully extubated, with
2/8 (25%) discharged on room air. Ex vivo analysis revealed significantly elevated
BTK activity, as evidenced by autophosphorylation, and increased IL-6 production
in blood monocytes from patients with severe COVID-19 compared with blood
monocytes from healthy volunteers. These results suggest that targeting excessive
host inflammation with a BTK inhibitor is a therapeutic strategy in severe
COVID-19 and has led to a confirmatory international prospective randomized
controlled clinical trial.

제 1편 코로나바이러스 정의
1. 코로나바이러스감염증-19(Covid-19) 정보 7
2. 코로나바이러스 분류 및 특성 9
3. 코로나바이러스 전자현미경 형태 11
4. 코로나바이러스 구조 (Covid-19 Organization) 13
5. 코로나19: 환경에 지속적인 영향을 미칠까? 19
6. 치료법(Therapeutical Method) 22

제 2편 연구논문
Inhibition of Bruton tyrosine kinase in patients with severe
COVID-19

1. Introduction 23
2. RESULTS 24
3. BTK Activation and IL-6 Production in Monocytes from
COVID-19 Patients 25
4. DISCUSSION 26
5. MATERIALS AND METHODS 28
6. Ethical Considerations 29
7. References 30