treatment with arbidol and moxifloxacin in ordinary and severe adult patients infected CORD-Papers-2021-10-25 (Version 1)

Title: Treatment with Arbidol and Moxifloxacin in Ordinary and Severe Adult Patients Infected with COVID-19
Abstract: Background An outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been widely spread. We aim to investigate the therapeutic effect of arbidol and moxifloxacin in patients infected with SARS-CoV-2. Methods We collected and analyzed data on 94 patients with COVID-19 including 27 severe patients at the Intensive Care Unit (ICU) and 74 ordinary patients at general isolation ward in Wuhan Xiehe Hospital, from February 15, 2020 to March 15, 2020. All patients were treated with arbidol (100mg each time, three times a day for 14 days) and moxifloxacin (0.4g each time, once a day for 7-14 days). Other data was also collected including demographic data, symptoms, laboratory findings, treatments and clinical outcomes. Results In basic characteristics, compared with the ordinary patients, the severe patients were older (median age was 63.0 years V.S 57.0 years, p=0.03), had higher proportion of hypertension (30% V.S 9%, p=0.03), higher possibility of getting fatigue and/or myalgia (26% V.S 6%, p=0.03), and had more obvious dyspnea symptom (26% V.S 3%, p=0.006). In regarding to laboratory results, we found the severe patients have higher white blood cell counts (p=0.003), neutrophil counts (p=0.007), higher levels of D-dimer (p<0.001), ALT (p<0.001) and AST (p=0.013) than the ordinary patients. After treatment of arbidol and moxifloxacin for one week, the rates of SARS-CoV-2 nucleic acid turning negative were 69.2% in the severe group and 77.8% in the ordinary group. A peculiar phenomenon was that IL-6 stands out among the cytokines in both groups, and higher in severe group than the ordinary one (p=0.011). After treating with arbidol and moxifloxacin for one week, IL-6 decreased significantly in severe group (p=0.023). Conclusion In summary, we proved the treatment of arbidol and moxifloxacin could be helpful in reducing viral load and inflammation during SARS-CoV2 infection, especially for negatively regulating fatal inflammation in severe COVID-19 patients. However, more evidence awaits further clinical verification.
Published: 6/5/2020
DOI: 10.1101/2020.05.30.20117598
DOI_URL: http://doi.org/10.1101/2020.05.30.20117598
Author Name: YU, D
Author link: https://covid19-data.nist.gov/pid/rest/local/author/yu_d
Author Name: SUN, S
Author link: https://covid19-data.nist.gov/pid/rest/local/author/sun_s
Author Name: LI, Y
Author link: https://covid19-data.nist.gov/pid/rest/local/author/li_y
Author Name: XI, W
Author link: https://covid19-data.nist.gov/pid/rest/local/author/xi_w
Author Name: JIN, D
Author link: https://covid19-data.nist.gov/pid/rest/local/author/jin_d
Author Name: SUN, K
Author link: https://covid19-data.nist.gov/pid/rest/local/author/sun_k
Author Name: YU, R
Author link: https://covid19-data.nist.gov/pid/rest/local/author/yu_r
Author Name: YAO, X
Author link: https://covid19-data.nist.gov/pid/rest/local/author/yao_x
Author Name: SONG, Z
Author link: https://covid19-data.nist.gov/pid/rest/local/author/song_z
Author Name: YANG, A
Author link: https://covid19-data.nist.gov/pid/rest/local/author/yang_a
Author Name: LUO, R
Author link: https://covid19-data.nist.gov/pid/rest/local/author/luo_r
Author Name: ZOU, B
Author link: https://covid19-data.nist.gov/pid/rest/local/author/zou_b
Author Name: LIU, Y
Author link: https://covid19-data.nist.gov/pid/rest/local/author/liu_y
sha: 7c447891580cdfc2e7f437d167f1eb35e9d319dd
license: medrxiv
source_x: MedRxiv; WHO
source_x_url: https://www.who.int/
url: https://doi.org/10.1101/2020.05.30.20117598 http://medrxiv.org/cgi/content/short/2020.05.30.20117598v1?rss=1
has_full_text: TRUE
Keywords Extracted from Text Content: AST blood cell COVID-19 patients coronavirus disease 2019 SARS-CoV-2 IL-6 COVID-19 neutrophil coronavirus 2 patients ALT SARS-CoV2 Wuhan Xiehe D-dimer SARS-CoV-2 nucleic acid moxifloxacin paramyxo leucocytes Guo arterial SARS-CoV-2 virus oxygen cellular membranes IgG IL-2 CD4 IgM IL-6 chest CD8 WN Xi Pecheur SARS-CoV-2 nucleic acid fluoroquinolone lassa viruses SARS-CoV-2 viral nucleic WBC medRxiv IL-4 throat swab specimens coronavirus H5N1 ×109/L blood cell COVID-19 patients COVID-19 cells aspartate aminotransferase CD3 HCV cardiovascular Wuhan Xiehe medRxiv preprint lopinavir/ritonavir IL-1 pharyngeal swab https://doi.org/10 phenylalanine liver hydroxychloroquine people lung SARS-CoV Fink IFN-γ serum SARS-CoV-2 IgG patients Mononuclear/macrophages Coronavirus Disease 2019 SARS-CoV-2 IgM https://doi.org/10.1101 chloroquine tryptophan AST IgG antibodies T ≥ TNF-α lymphocytes pulmonary SARS-CoV-2 alanine aminotransferase SARS-CoV-2 IgG/IgM antibody P=0.011 neutrophils patient IL-10 IL-6、IL-8、IL-10 YHLO COVID-19 virus ALT blood D-dimer Shenzhen moxifloxacin Moxifloxacin https://doi.org/10.1101/2020.05.30.20117598 doi UK IFN-α/-β Babiuk K Sun EBOV
Extracted Text Content in Record: First 5000 Characters:Background An outbreak of coronavirus disease 2019 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been widely spread. We aim to investigate the therapeutic effect of arbidol and moxifloxacin in patients infected with SARS-CoV-2. We collected and analyzed data on 94 patients with COVID-19 including 27 severe patients at the Intensive Care Unit (ICU) and 74 ordinary patients at general isolation ward in Wuhan Xiehe Hospital, from February 15, 2020 to March 15, 2020. All patients were treated with arbidol (100mg each time, three times a day for 14 days) and moxifloxacin (0.4g each time, once a day for 7-14 days). Other data was also collected including demographic data, symptoms, laboratory findings, treatments and clinical outcomes. In basic characteristics, compared with the ordinary patients, the severe patients were older (median age was 63.0 years V.S 57.0 years, p=0.03), had higher proportion of hypertension (30% V.S 9%, p=0.03), higher possibility of getting fatigue and/or myalgia (26% V.S 6%, p=0.03), and had more obvious dyspnea symptom (26% V.S 3%, p=0.006). In regarding to laboratory results, we found the severe patients have higher white blood cell counts (p=0.003), neutrophil counts (p=0.007), higher levels of D-dimer (p<0.001), ALT (p<0.001) and AST (p=0.013) than the ordinary patients. After treatment of arbidol and moxifloxacin for one week, the rates of SARS-CoV-2 nucleic acid turning negative were 69.2% in the severe group and 77.8% in the ordinary group. A peculiar phenomenon was that IL-6 stands out among the cytokines in both groups, and higher in severe group than the ordinary one (p=0.011). After treating with arbidol and moxifloxacin for one week, IL-6 decreased significantly in severe group (p=0.023). In summary, we proved the treatment of arbidol and moxifloxacin could be helpful in reducing viral load and inflammation during SARS-CoV2 infection, especially for negatively regulating fatal inflammation in severe COVID-19 patients. However, more evidence awaits further clinical verification. A novel coronavirus designated as SARS-CoV-2 has been known causing an international outbreak of respiratory illness named COVID-19 (Huang et al., 2020; Wang et al., 2020) . Up to May 31,2020,more than 5.75 million people in worldwide has been confirmed with COVID-19, at least 361 thousand patients died (Johns Hopkins University -https://coronavirus.jhu.edu/map.html). Effective and specific treatment for COVID-19 is the most urgent task at the moment. Up to now, there is still no specific treatment for SARS-CoV-2 infection. Several drugs, such as chloroquine, hydroxychloroquine, lopinavir/ritonavir, have shown some effects in treating COVID-19 (Huang et al., 2020; Meo et al., 2020; Wang et al., 2020) , however also come along with serious side effects. Arbidol is a synthetic broad-spectrum antiviral agent that is used to treat many virus infections in both clinic and experimental research, such as seasonal influenza, ebola virus, SARS-CoV, lassa viruses and paramyxo (Shi et al., 2007; Blaising et al., 2013; Blaising et al., 2014b; Pecheur et al., 2016) . So far, little is known about application of abidor in the treatment of COVID-19. Moxifloxacin is a fourth-generation fluoroquinolone with expanded active against a wide range of aerobic gram-positive and gram-negative organisms, which is commonly used and suitable for respiratory bacterial infection (Ding and Zhang, 2018) . To date, clinical evidence on arbidol and moxifloxacin in patients with COVID-19 is limited. Herein, we evaluated the therapeutic effects of arbidol and moxifloxacin in patients with COVID-19. We included 67 ordinary patients at general isolation ward and 27 severe patients at the Intensive Care Unit (ICU) from Wuhan Xiehe Hospital (admission data from February 15 to March 15). COVID-19 was clinically diagnosed as "viral pneumonia" based on clinical symptoms, epidemiological exposure history, chest computed tomographic (CT) scan and real-time reverse transcription-polymerase chain reaction . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted June 5, 2020 . . https://doi.org/10.1101 (RT-PCR) assay for SARS-CoV-2 from throat swab specimens. Clinical stage of the patients was classified according to "Interim Guidance for Diagnosis and Treatment of Coronavirus Disease 2019 (the 6th edition)" released by National Health Commission. Severe COVID-19 was defined when patients got one of the following criteria: (1) respiratory frequency ≥ 30 times/min; (2) oxygen saturation < 93% at rest; (3) arterial partial pressure of oxygen (PaO2)/oxygen concentration (FiO2) ≤ 300 mmHg (1 mmHg = 0.133 kPa). SARS-CoV-2 viral nucleic acid was detected by RT-PCR assay from pharyngeal swab specimens of the patients at W
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