key: cord-0741524-m762124j
authors: Xu, Ping; Huang, Jianping; Fan, Zhao; Huang, Wendi; Qi, Minghua; Lin, Xuwen; Song, Weidong; Yi, li
title: Arbidol/IFN-α2b Therapy for Patients With Corona Virus Disease 2019: A Retrospective Multicenter Cohort Study
date: 2020-05-20
journal: Microbes Infect
DOI: 10.1016/j.micinf.2020.05.012
sha: c1c4cb5d51bea61374ef83518a90cd4cae81d1f4
doc_id: 741524
cord_uid: m762124j

The spread of COVID-19 is accelerating. At present, there is no specific antiviral drugs for COVID-19 outbreak. This is a multicenter retrospective cohort study of patients with laboratory-confirmed COVID-19 infection pneumonia from 3 hospitals in Hubei and Guangdong province, 141 adults (aged ≥18 years) without ventilation were included. Combined group patients were given Arbidol and IFN-α2b, monotherapy group patients inhaled IFN-α2b for 10-14 days. Of 141 COVID-19 patients, baseline clinical and laboratory characteristics were similar between combined group and monotherapy group, that 30% of the patients leucocytes counts were below the normal range and 36.4% of the patients experienced lymphocytopenia. The duration of viral RNA of respiratory tract in the monotherapy group was not longer than that in the combined therapy group. There was no significant differences between two groups. The absorption of pneumonia in the combined group was faster than that in the monotherapy group. We inferred that Arbidol/IFN - 2b therapy can be used as an effective method to improve the COVID-19 pneumonia of mild patients, although it helpless with accelerating the virus clearance. These results should be verified in a larger prospective randomized environment.

were included. Combined group patients were given Arbidol and IFN-α2b, 22 monotherapy group patients inhaled IFN-α2b for 10-14 days. Of 141 COVID-19 23 patients, baseline clinical and laboratory characteristics were similar between 24 combined group and monotherapy group, that 30% of the patients leucocytes counts 25

were below the normal range and 36.4% of the patients experienced lymphocytopenia. 26

The duration of viral RNA of respiratory tract in the monotherapy group was not 27 longer than that in the combined therapy group. There was no significant differences 28 between two groups. The absorption of pneumonia in the combined group was faster 29 than that in the monotherapy group. We inferred that Arbidol/IFN -2b therapy can be 30 used as an effective method to improve the COVID-19 pneumonia of mild patients, 31

although it helpless with accelerating the virus clearance. These results should be 32 no vaccine or specific antiviral therapies for human and animal coronavirus (COV) 42

[2]. 43

The current management of COVID-19 is mainly supportive, some rIFN-α2b, rIFN-β1a, and rIFN-β1b) were active against MERS-CoV in vitro [5] . 52

Interferon-α treatment strongly inhibite severe in vitro cytopathology induced by 53 MERS-coronavirus replication. Furthermore, MERS-CoV was found to be 50-100 54 times more sensitive to alpha interferon (IFN-α) treatment than SARS-CoV in vitro. 55

These findings highlight relevant differences between these distantly related CoVs in 56 terms of their interaction with and evasion of the cellular innate immune 57 

Epidemiological , clinical, laboratory, imaging data, management, and clinical 93 outcomes data were collected through a review of medical records. According to 94 distribution of the affected lung parenchyma , the severity of total lung lobes was 95 evaluated and classified score according to CT scan[12]:0 as normal, 1 as < 25% 96 abnormality, 2 as 25-50% abnormality, 3 as 50-75% abnormality, and 4 as > 75% 97 abnormality. 98

Treatment protocols was Arbidol/IFN-α2b combination, IFN-α2b alone. 

Between January 2019 and Mar 2020, a total of 221 hospitalized patients, with 139 laboratory-confirmed COVID-19 infection pneumonia without invasive ventilation 140 were screened. All patients treated with Arbidol/IFN-α2b or IFN-α2b. we excluded 141 the ones that did not meet the eligibility criteria. 74 cases among them were treated 142 with other antiviral drugs, such as ribavirin, zanamivir, chloroquine, lopinavir/ treatment course (3 patients needed invasive mechanical ventilation and 2 patients 146 died for pneumonia progress), so 5 patients were excluded, 141patients were included 147 in the multicenter cohort study. as shown in Figure. (Table 1) . Chest imaging showed ground-glass opacity, multiple 163 patchs-like shadows and consolidation in the lungs. There was no significant 3.3 In this study, there were no significant differences between hospitalization 166 and RNA clearance days with respect to age, sex, symptoms After treatment for 7-14 167 days, there was no statistically differences of the viral RNA clearance days between 168 two group ( Figure. (Table 1) . 175

The median hospitalization days was 27.1 vs. 24.2 days in two group (P=0.056). 176

There was no significant differences between two groups ( Figure. CT and symptom improvement was significantly shorter than that of nucleic acid 180 conversion negative. CT absorption time was16.7 days vs.19.8 days, respectively; P 181 =0.037 (Table 1) , the improvement rate of CT and symptoms was faster than that of 182 nucleic acid clearance.The absorption of pneumonia in the combined group was faster 183 than that in the monotherapy group. Only 3 patients in IFN-α2b group, the time of 184 virus turning negative is shorter than that of clinical symptoms and CT improved. 185

These symptoms were neurogenic bladder caused dysuria and exertional dyspnea. and CT, but also RNA is negative in two consecutive tests. In our study, specimens 226 taken from oropharyngeal/nasopharynxswabs/sputum for RT-PCR RNA test , the 227 median time from the onset of symptoms to 2 occasions negative RT-PCR results was 23.8(8-53) days in IFN-α2b group, 27.4 (11-53) days in combined group respectly, 229 presenting notable individual differences in patients regardless age, sex,underly 230 disease, It is suggested that it will take a long time for nucleic acids to be removed 231 from the respiratory tract. During this period, patients who expel the virus may 232 become a potential source of infection, the quantity and activity of virus are important 233 infectious factors. 234

For most patients in our study, CT improvement more sooner than the nucleic acid 235 clearance. The median CT improvement days of combination group less than that of 236 monotherapy group (19.8 days of monotherapy group vs.16.7days of combined group, 237 P =0.037) , The data suggested that Arbidol combined IFN-α2b versus IFN-α2b alone 238 could have potential benefits on inhibiting COVID-19 lung inflammation of mild 239 cases without invasive ventilation, but no benefits on RNA clearance, and we find 240

Abidol and IFN-α2b therapy were well tolerated by the treatment group with no 241 premature discontinuation secondary to adverse effects. 242

Our study is limited by its retrospective non-randomised control, there may be a 243 potential selection bias. It should be noted that there were 5 patients received IFN-α2b 244 alone treatment for 2-4 days were excluded because of the invasive ventilation or 245 death due to deterioration. It was difficult to assess whether the aggravation is related 246 to the difference of drug treatment. So we removed the five individuals to avoid 247 potentially detrimental to clinical outcome, but it is difficult to completely avoid

In conclusion, Arbidol in combination with IFN-α2b was no effective in 250 COVID-19 RNA clearence and hospitalization than IFN-α2b monotherapy in this 251 cohort, but accelerate pneumonia absorption, but these results should be verified in a 252 larger prospective randomized setting. 253

The authors thank the Jianli People Hospital，Jianli Traditional Chinese medicine 255

Hospital and Peking University Shenzhen Hospital for its support in the database 256 construction. This work was supported by the Natural Science Foundation of 257 

A novel coronavirus from 262 patients with pneumonia in China

Drug treatment options for the 2019-new coronavirus (2019-nCoV)

IFN-α2a or IFN-β1a in combination with ribavirin to treat Middle East 271 respiratory syndrome coronavirus pneumonia: a retrospective study

Interferon-β and mycophenolic acid are potent inhibitors of Middle East 275 respiratory syndrome coronavirus in cell-based assays

MERS-coronavirus replication induces severe in vitro 279 cytopathology and is strongly inhibited by cyclosporin A or interferon-α 280 treatment

Inhibition of the infectivity 282 and inflammatory response of influenza virus by Arbidol hydrochloride in vitro 283 and in vivo (mice and ferret)

Arbidol as a broad-spectrum antiviral: an 285 update

The antiviral activity of 287 arbidol hydrochloride against herpes simplex virus type II (HSV-2) in a mouse 288 model of vaginitis

Recent developments in anti-severe acute respiratory 311 syndrome coronavirus chemotherapy

Abelson kinase inhibitors are potent inhibitors of severe acute respiratory 314 syndrome coronavirus and middle east respiratory syndrome coronavirus fusion

LPV/r versus LPV/r alone against Corona Virus Disease 2019: A retrospective 318 cohort study

The authors declare no conflict of interest. 260