Abstract: Background: Currently, there are no drugs that have been proven to be effective against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Because of its broad antiviral activity, interferon (IFN) should be evaluated as a potential therapeutic agent for treatment of coronavirus disease 2019 (COVID-19), especially while COVID-19-specific therapies are still under development. Methods: Confirmed COVID-19 patients hospitalized in the First Affiliated Hospital, School of Medicine, Zhejiang University in Hangzhou, China, from January 19 to February 19, 2020 were enrolled in a retrospective study. The patients were separated into an IFN group and a control group according to whether they received initial IFN-α2b inhalation treatment after admission. Propensity-score matching was used to balance the confounding factors. Results: A total of 104 confirmed COVID-19 patients, 68 in the IFN group and 36 in the control group, were enrolled. Less hypertension (27.9% vs. 55.6%, P=0.006), dyspnea (8.8% vs. 25.0%, P=0.025), or diarrhea (4.4% vs. 19.4%, P=0.030) was observed in the IFN group. Lower levels of albumin and C-reactive protein and higher level of sodium were observed in the IFN group. Glucocorticoid dosage was lower in the IFN group (median, 40 vs. 80 mg/d, P=0.025). Compared to the control group, fewer patients in the IFN group were ventilated (13.2% vs. 33.3%, P=0.015) and admitted to intensive care unit (ICU) (16.2% vs. 44.4%, P=0.002). There were also fewer critical patients in the IFN group (7.4% vs. 25.0%, P=0.017) upon admission. Although complications during admission process were comparable between groups, the discharge rate (85.3% vs. 66.7%, P=0.027) was higher and the hospitalization time (16 vs. 21 d, P=0.015) was shorter in the IFN group. When other confounding factors were not considered, virus shedding time (10 vs. 13 d, P=0.014) was also shorter in the IFN group. However, when the influence of other factors was eliminated using propensity score matching, virus shedding time was not significantly shorter than that of the control group (12 vs. 15 d, P=0.206). Conclusions: IFN-α2b spray inhalation did not shorten virus shedding time of SARS-CoV-2 in hospitalized patients.

干扰素-α2b喷雾吸入未缩短住院患者的SARS-CoV-2的脱落时间:一项初步的配对病例对照研究

[1]Alhazzani W, Møller MH, Arabi YM, et al., 2020. Surviving sepsis campaign: guidelines on the management of critically ill adults with coronavirus disease 2019 (COVID-19). Intensive Care Med, 46(5):854-887.

[2]Al-Tawfiq JA, Momattin H, Dib J, et al., 2014. Ribavirin and interferon therapy in patients infected with the Middle East respiratory syndrome coronavirus: an observational study. Int J Infect Dis, 20:42-46.

[3]Arabi YM, Shalhoub S, Mandourah Y, et al., 2020. Ribavirin and interferon therapy for critically ill patients with Middle East respiratory syndrome: a multicenter observational study. Clin Infect Dis, 70(9):1837-1844.

[4]Cao B, Wang YM, Wen DN, et al., 2020. A trial of lopinavir-ritonavir in adults hospitalized with severe COVID-19. N Engl J Med, 382(19):1787-1799.

[5]Chan JFW, Yao YF, Yeung ML, et al., 2015. Treatment with lopinavir/ritonavir or interferon-β1b improves outcome of MERS-CoV infection in a nonhuman primate model of common marmoset. J Infect Dis, 212(12):1904-1913.

[6]Channappanavar R, Fehr AR, Vijay R, et al., 2016. Dysregulated type I interferon and inflammatory monocyte-macrophage responses cause lethal pneumonia in SARS-CoV-infected mice. Cell Host Microbe, 19(2):181-193.

[7]Cinatl J, Morgenstern B, Bauer G, et al., 2003. Treatment of SARS with human interferons. Lancet, 362(9380):293-294.

[8]Cinatl J Jr, Michaelis M, Scholz M, et al., 2004. Role of interferons in the treatment of severe acute respiratory syndrome. Expert Opin Biol Ther, 4(6):827-836.

[9]Danesh A, Cameron CM, León AJ, et al., 2011. Early gene expression events in ferrets in response to SARS coronavirus infection versus direct interferon-alpha2b stimulation. Virology, 409(1):102-112.

[10]Dusheiko G, 1997. Side effects of α interferon in chronic hepatitis C. Hepatology, 26(S3):112s-121s.

[11]Falzarano D, de Wit E, Martellaro C, et al., 2013a. Inhibition of novel β coronavirus replication by a combination of interferon-α2b and ribavirin. Sci Rep, 3:1686.

[12]Falzarano D, de Wit E, Rasmussen AL, et al., 2013b. Treatment with interferon-α2b and ribavirin improves outcome in MERS-CoV-infected rhesus macaques. Nat Med, 19(10):1313-1317.

[13]Ge ZY, Yang LM, Xia JJ, et al., 2020. Possible aerosol transmission of COVID-19 and special precautions in dentistry. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 21(5):361-368.

[14]Haagmans BL, Kuiken T, Martina BE, et al., 2004. Pegylated interferon-α protects type 1 pneumocytes against SARS coronavirus infection in macaques. Nat Med, 10(3):290-293.

[15]Kellum JA, Lameire N, Aspelin P, et al., 2012. Kidney disease: improving global outcomes (KDIGO) acute kidney injury work group. KDIGO clinical practice guideline for acute kidney injury. Kidney Int Suppl, 2(1):1-138.

[16]Li GD, de Clercq E, 2020. Therapeutic options for the 2019 novel coronavirus (2019-nCoV). Nat Rev Drug Discov, 19(3):149-150.

[17]Li HO, Zhou YJ, Zhang M, et al., 2020. Updated approaches against SARS-CoV-2. Antimicrob Agents Chemother, 64(6):e00483-20.

[18]Lu CW, Liu XF, Jia ZF, 2020. 2019-nCoV transmission through the ocular surface must not be ignored. Lancet, 395(10224):e39.

[19]Mantlo E, Bukreyeva N, Maruyama J, et al., 2020. Potent antiviral activities of type I interferons to SARS-CoV-2 infection. bioRxiv, preprint.

[20]National Health Commission of the People’s Republic of China, 2020. Chinese management guideline for COVID-19 (Version 7.0). http://www.nhc.gov.cn/yzygj/s7653p/202003/46c9294a7dfe4cef80dc7f5912eb1989.shtml [Accessed on Mar. 4, 2020] (in Chinese).

[21]Omrani AS, Saad MM, Baig K, et al., 2014. Ribavirin and interferon alfa-2a for severe Middle East respiratory syndrome coronavirus infection: a retrospective cohort study. Lancet Infect Dis, 14(11):1090-1095.

[22]Ren WB, Xia XJ, Huang J, et al., 2019. Interferon-γ regulates cell malignant growth via the c-Abl/HDAC2 signaling pathway in mammary epithelial cells. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 20(1):39-48.

[23]Shi Y, Wang G, Cai XP, et al., 2020. An overview of COVID-19. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 21(5):343-360.

[24]Spiegel M, Pichlmair A, Martínez-Sobrido L, et al., 2005. Inhibition of beta interferon induction by severe acute respiratory syndrome coronavirus suggests a two-step model for activation of interferon regulatory factor 3. J Virol, 79(4):2079-2086.

[25]Thiel V, Weber F, 2008. Interferon and cytokine responses to SARS-coronavirus infection. Cytokine Growth Factor Rev, 19(2):121-132.

[26]van Doremalen N, Bushmaker T, Morris DH, et al., 2020. Aerosol and surface stability of SARS-CoV-2 as compared with SARS-CoV-1. N Engl J Med, 382(16):1564-1567.

[27]World Health Organization, 2020. Clinical management of severe acute respiratory infection when novel coronavirus (nCoV) infection is suspected: interim guidance. https:// apps.who.int/iris/handle/10665/330854 [Accessed on Feb. 20, 2020].

[28]Wu ZY, McGoogan JM, 2020. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention. JAMA, 323(13):1239-1242.

[29]Zhu N, Zhang DY, Wang WL, et al., 2020. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med, 382(8):727-733.