First Clinical Study Using HCV Protease Inhibitor Danoprevir to Treat Naive and Experienced COVID-19 Patients

Hongyi Chen; Zhicheng Zhang; Li Wang; Zhihua Huang; Fanghua Gong; Xiaodong Li; Yahong Chen; Jinzi J. WU

The copyright holder for this preprint . https://doi.org/10.1101/2020.03.22.20034041 doi: medRxiv preprint patient was switched to danoprevir boosted by ritonavir, along with interferon nebulization. On February 18, patient had a weak positive RT-PCR test for viral RNA in nasal swab.  On February 20, 4 days after receiving danoprevir boosted by ritonavir treatment, the right lower lung showed shrunken patch-shape areas and decreased density of GGO ( Figure 3C ). On the same day, RT-PCR test with the nasal swab became negative and remained negative at the next day RT-PCR test.  In the morning of February 23, the patient received the last dose of danoprevir boosted by ritonavir treatment. Since he met all four discharge standards described in Methods section, the patient was discharged from the hospital on the same day. Five patients failed lopinavir/ritonavir plus interferon nebulization and switched to danoprevir/ritonavir without interferon nebulization. The medical history, treatment and various examinations for one of patients, patient 8, were described in details below.  On February 9, a woman in her 40's, who was a permanent resident in Wuhan City, was admitted to the hospital due to maximum BT 38℃ and RT-PCR positive SARS-CoV-2 in nasal swab. She had occasional coughs with white sputum. The vital sign of the patient showed BT of 37.4℃ and SPO2 of 99% under ambient air. The patient had half-year history of hypertension. The patient was given the first dose of lopinavir/ritonavir, 2 tablets at a time, twice per day, along with interferon nebulization in the evening of February 9.  On February 10, based on CT scans, subpleural areas of both lower lungs and the tongue-like segment of the left lung showed GGO and patch-shape areas ( Figure 4A ). From February 10 to February 13, the patient showed slightly fluctuating BT (maximum 37.3℃ to minimum 36.4℃), coughs with white sputum, anorexia and diarrhea with yellow thin stool. The laboratory results revealed leukopenia (3.40 ×10 9 /L) and lymphopenia (0.7 ×10 9 /L) ( Table 3) .  On February 13, 4 days after receiving lopinavir/ritonavir treatment, GGO and patch-shape areas showed a slightly higher density ( Figure 4B ) compared to previous CT image on February 10.  On February 17, 8 days after receiving lopinavir/ritonavir treatment, the patient reported improved appetite and sleeping while coughing with white sputum remained. CT scan showed that no significant changes were obat served compared to previous CT image on February 13 and the opacities at tongue-like segment increased ( Figure 4C ).  On February 19, the patient received the last dose of lopinavir/ritonavir and interferon nebulization. The treatment duration of both lopinavir/ritonavir and interferon nebulization exceeded the recommendation by China National Standards [14] . As a result, both lopinavir/ritonavir and interferon nebulization were stopped.  On February 20, she was switched to danoprevir boosted by ritonavir without interferon nebulization .  On February 22, 3-day after receiving danoprevir/ritonavir treatment, RT-PCR test was negative in both nasal and phlegm swabs.  On February 23, 4 days after switching to danoprevir boosted by ritonavir, the patient showed improved white blood cell count (4.31 × 10 9 /L) ( Table 3) . CT scans showed GGO and patch-shape areas decreased in density compared to previous CT images on February 17, indicating absorption in both lungs ( Figure 4D ).  On February 25, the pati