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- ÀúÀÚMark Roschewski, Michail S. Lionakis, Jeff P.Sharman, Joseph Roswarski, Andre Goy5,¿Ü Àú
- ÃâÆÇ»ç¾ÆÁø
- ÃâÆÇÀÏ2020-07-12
- µî·ÏÀÏ2020-12-21
- SNS°øÀ¯
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Patients with severe COVID-19 have a hyperinflammatory immune responsesuggestive 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.
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Á¦ 1Æí Äڷγª¹ÙÀÌ·¯½º Á¤ÀÇ1. Äڷγª¹ÙÀÌ·¯½º°¨¿°Áõ-19(Covid-19) Á¤º¸ 7
2. Äڷγª¹ÙÀÌ·¯½º ºÐ·ù ¹× Ư¼º 9
3. Äڷγª¹ÙÀÌ·¯½º ÀüÀÚÇö¹Ì°æ ÇüÅ 11
4. Äڷγª¹ÙÀÌ·¯½º ±¸Á¶ (Covid-19 Organization) 13
5. Äڷγª19: ȯ°æ¿¡ Áö¼ÓÀûÀÎ ¿µÇâÀ» ¹ÌÄ¥±î? 19
6. Ä¡·á¹ý(Therapeutical Method) 22
Á¦ 2Æí ¿¬±¸³í¹®
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