Favipiravir in the treatment of patients with SARS-CoV-2 RNA recurrent positive after discharge: a multicenter, open-label, randomized trial
et al., International Immunopharmacology, doi:10.1016/j.intimp.2021.107702, Apr 2021
RCT with 55 patients (36 favipiravir, 19 control) who were PCR+ after recovery, showing improved viral clearance with treatment.
Potential risks of favipiravir include kidney injury1-3, liver injury2-4, and mutagenicity, carcinogenicity, teratogenicity, embryotoxicity, and the creation of dangerous variants5-11.
Standard of Care (SOC) for COVID-19 in the study country,
China, is average with moderate efficacy for approved treatments12.
|
risk of no viral clearance, 59.0% lower, RR 0.41, p = 0.06, treatment 7 of 36 (19.4%), control 9 of 19 (47.4%), NNT 3.6.
|
|
time to viral-, 52.4% lower, relative time 0.48, p = 0.04, treatment 36, control 19, inverted to make RR<1 favor treatment.
|
| Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates |
1.
Abdulaziz et al., Clinical Features and Prognosis of Acute Kidney Injury in Hospital-Admitted Patients with COVID-19 in Egypt: A Single-Center Experience, Mansoura Medical Journal, doi:10.58775/2735-3990.1433.
2.
Ülger et al., Experimental evaluation of favipiravir (T-705)-induced liver and kidney toxicity in rats, Food and Chemical Toxicology, doi:10.1016/j.fct.2025.115472.
3.
El-Fetouh et al., Experimental Studies on Some Drugs Used in Covid-19 Treatment (Favipiravir and Dexamethasone) in Albino Rats, Journal of Advanced Veterinary Research, 13:10, www.advetresearch.com/index.php/AVR/article/view/1635.
4.
Almutairi et al., Liver Injury in Favipiravir-Treated COVID-19 Patients: Retrospective Single-Center Cohort Study, Tropical Medicine and Infectious Disease, doi:10.3390/tropicalmed8020129.
5.
Zhirnov et al., Favipiravir: the hidden threat of mutagenic action, Journal of microbiology, epidemiology and immunobiology, doi:10.36233/0372-9311-114.
6.
Waters et al., Human genetic risk of treatment with antiviral nucleoside analog drugs that induce lethal mutagenesis: the special case of molnupiravir, Environmental and Molecular Mutagenesis, doi:10.1002/em.22471.
7.
Hadj Hassine et al., Lethal Mutagenesis of RNA Viruses and Approved Drugs with Antiviral Mutagenic Activity, Viruses, doi:10.3390/v14040841.
8.
Shum, C., An investigational study into the drug-associated mutational signature in SARS-CoV-2 viruses, The University of Hong Kong, PhD Thesis, hub.hku.hk/handle/10722/344396.
9.
Shiraki et al., Convenient screening of the reproductive toxicity of favipiravir and antiviral drugs in Caenorhabditis elegans, Heliyon, doi:10.1016/j.heliyon.2024.e35331.
10.
Cenikli et al., Does Favipiravir interact with DNA? Design of electrochemical DNA nanobiosensor to investigate the interaction between DNA and Favipiravir used in the treatment of COVID-19, Talanta, doi:10.1016/j.talanta.2025.128084.
Zhao et al., 21 Apr 2021, Randomized Controlled Trial, China, peer-reviewed, 25 authors, study period 27 March, 2020 - 9 May, 2020.
Favipiravir in the treatment of patients with SARS-CoV-2 RNA recurrent positive after discharge: A multicenter, open-label, randomized trial
International Immunopharmacology, doi:10.1016/j.intimp.2021.107702
Background: The clinical characteristics and treatment of patients who tested positive for COVID-19 after recovery remained elusive. Effective antiviral therapy is important for tackling these patients. We assessed the efficacy and safety of favipiravir for treating these patients. Methods: This is a multicenter, open-label, randomized controlled trial in SARS-CoV-2 RNA re-positive patients. Patients were randomly assigned in a 2:1 ratio to receive either favipiravir, in addition to standard care, or standard care alone. The primary outcome was time to achieve a consecutive twice (at intervals of more than 24 h) negative RT-PCR result for SARS-CoV-2 RNA in nasopharyngeal swab and sputum sample. Results: Between March 27 and May 9, 2020, 55 patients underwent randomization; 36 were assigned to the favipiravir group and 19 were assigned to the control group. Favipiravir group had a significantly shorter time from start of study treatment to negative nasopharyngeal swab and sputum than control group (median 17 vs. 26 days); hazard ratio 2.1 (95% CI [1.1-4.0], p = 0.038). The proportion of virus shedding in favipiravir group was higher than control group (80.6% [29/36] vs. 52.6% [10/19], p = 0.030, respectively). C-reactive protein decreased significantly after treatment in the favipiravir group (p = 0.016). The adverse events were generally mild and self-limiting. Conclusion: Favipiravir was safe and superior to control in shortening the duration of viral shedding in SARS-CoV-2 RNA recurrent positive after discharge. However, a larger scale and randomized, double-blind, placebocontrolled trial is required to confirm our conclusion.
consent form.
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Appendix A. Supplementary material Supplementary data to this article can be found online at https://doi. org/10.1016/j.intimp.2021.107702.
References
An, Liao, Xiao, Qian, Yuan et al., Clinical characteristics of the recovered COVID-19 patients with re-detectable positive RNA test, medRxiv
Bai, Mu, Kargbo, Song, Niu et al., Clinical and Virological Characteristics of Ebola Virus Disease Patients Treated With Favipiravir (T-705)-Sierra Leone, Clin. Infect. Dis
Beigel, Tomashek, Dodd, Mehta, Zingman et al., Remdesivir for the Treatment of Covid-19 -Preliminary Report, New Engl. J. Med
Cai, Yang, Liu, Chen, Shu et al., Experimental Treatment with Favipiravir for COVID-19: An Open-Label Control Study
Cao, Wang, Wen, Liu, Wang et al., A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19, N. Engl. J. Med
Chen, Zhang, Yang, Wang, Zhai et al., Fangcang shelter hospitals: a novel concept for responding to public health emergencies, Lancet
Coomes, HaghbayanFavipiravir, an antiviral for COVID-19?, J. Antimicrobial Chemotherapy
Diao, Wang, Tan, Chen, Liu et al., Reduction and Functional Exhaustion of T Cells in Patients With Coronavirus Disease 2019 (COVID-19), Front. Immunol
Geleris, Sun, Platt, Zucker, Baldwin et al., Observational Study of Hydroxychloroquine in Hospitalized Patients with Covid-19, New Engl. J. Med
Grubaugh, Hanage, Rasmussen, Making sense of mutation: what D614G means for the COVID-19 pandemic remains unclear, Cell
Hong, Cao, Liu, Lin, Zhou et al., Prolonged presence of viral nucleic acid in clinically recovered COVID-19 patients was not associated with effective infectiousness, Emerg. Microbes. Infect
Hung, Lung, Tso, Liu, Chung et al., Triple combination of interferon beta-1b, lopinavir-ritonavir, and ribavirin in the treatment of patients admitted to hospital with COVID-19: an open-label, randomised, phase 2 trial, Lancet
Korber, Fischer, Gnanakaran, Yoon, Theiler et al., Tracking changes in SARS-CoV-2 Spike: evidence that D614G increases infectivity of the COVID-19 virus, Cell
Lan, Xu, Ye, Xia, Wang et al., Positive RT-PCR Test Results in Patients Recovered From COVID-19, JAMA
Li, Guan, Wu, Wang, Zhou et al., Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia, New Engl. J. Med
Li, Zhang, Wu, Wang, Zhao, The Mechanism and Clinical Outcome of patients with Corona Virus Disease 2019 Whose Nucleic Acid Test has changed from negative to positive, and the therapeutic efficacy of Favipiravir: A structured summary of a study protocol for a randomised controlled trial, Trials
Ling, Xu, Lin, Tian, Zhu et al., Persistence and clearance of viral RNA in 2019 novel coronavirus disease rehabilitation patients, Chin. Med. J
Mei, Li, Du, Yuan, Li et al., Assessment of patients who tested positive for COVID-19 after recovery, Lancet Infect. Dis
Pan, Kok, Eikelenboom, Horsfall, Jörg et al., The mental health impact of the COVID-19 pandemic on people with and without depressive, anxiety, or obsessive-compulsive disorders: a longitudinal study of three Dutch case-control cohorts, Lancet Psychiatry
Qu, Kang, Cong, Positive result of Sars-Cov-2 in sputum from a cured patient with COVID-19, Travel Med. Infect. Dis
Song, Fu, Liu, Luo, Wang et al., Mental health status of medical staff in emergency departments during the Coronavirus disease 2019 epidemic in China, Brain Behav. Immun
Tang, Cao, Han, Wang, Chen et al., Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: open label, randomised controlled trial, BMJ (Clinical research ed
Tang, Wu, Li, Song, Yao et al., On the origin and continuing evolution of SARS-CoV-2, Natl. Sci. Rev
Vijayvargiya, Esquer Garrigos, Almeida, Gurram, Stevens et al., Treatment Considerations for COVID-19: A Critical Review of the Evidence (or Lack Thereof), Mayo Clin. Proc
Wang, Cao, Zhang, Yang, Liu et al., Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro, Cell Res
Wang, Zhang, Du, Du, Zhao et al., Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial, Lancet
Yang, Jiang, Wang, Tang, Fang et al., Viral RNA level, serum antibody responses, and transmission risk in recovered COVID-19 patients with recurrent positive SARS-CoV-2 RNA test results: a population-based observational cohort study, Emerg. Microbes. Infect
Yao, He, Li, Zhang, Wang et al., Pathological evidence for residual SARS-CoV-2 in pulmonary tissues of a ready-for-discharge patient, Cell Res
Zhou, Liu, Liu, Cause analysis and treatment strategies of "recurrence" with novel coronavirus pneumonia (COVID-19) patients after discharge from hospital (in Chinese), Chin. J. Tuberculosis Respiratory Dis
DOI record:
{
"DOI": "10.1016/j.intimp.2021.107702",
"ISSN": [
"1567-5769"
],
"URL": "http://dx.doi.org/10.1016/j.intimp.2021.107702",
"alternative-id": [
"S1567576921003386"
],
"article-number": "107702",
"assertion": [
{
"label": "This article is maintained by",
"name": "publisher",
"value": "Elsevier"
},
{
"label": "Article Title",
"name": "articletitle",
"value": "Favipiravir in the treatment of patients with SARS-CoV-2 RNA recurrent positive after discharge: A multicenter, open-label, randomized trial"
},
{
"label": "Journal Title",
"name": "journaltitle",
"value": "International Immunopharmacology"
},
{
"label": "CrossRef DOI link to publisher maintained version",
"name": "articlelink",
"value": "https://doi.org/10.1016/j.intimp.2021.107702"
},
{
"label": "Content Type",
"name": "content_type",
"value": "article"
},
{
"label": "Copyright",
"name": "copyright",
"value": "© 2021 Published by Elsevier B.V."
}
],
"author": [
{
"affiliation": [],
"family": "Zhao",
"given": "Hong",
"sequence": "first"
},
{
"affiliation": [],
"family": "Zhang",
"given": "Chi",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Zhu",
"given": "Qi",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Chen",
"given": "Xianxiang",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Chen",
"given": "Guilin",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Sun",
"given": "Wenjin",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Xiao",
"given": "Zuohan",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Du",
"given": "Weijun",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Yao",
"given": "Jing",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Li",
"given": "Guojun",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Ji",
"given": "Yanhua",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Li",
"given": "Niuniu",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Jiang",
"given": "Yujin",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Wang",
"given": "Ying",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Zeng",
"given": "Qingjin",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Li",
"given": "Wei",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Gong",
"given": "Beilei",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Chang",
"given": "Xianyou",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Zhu",
"given": "Feng",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Jiang",
"given": "Xiufeng",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Li",
"given": "Jiawen",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Wu",
"given": "Zhao",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Liu",
"given": "Yingxia",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Peng",
"given": "Peng",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Wang",
"given": "Guiqiang",
"sequence": "additional"
}
],
"container-title": "International Immunopharmacology",
"container-title-short": "International Immunopharmacology",
"content-domain": {
"crossmark-restriction": true,
"domain": [
"elsevier.com",
"sciencedirect.com"
]
},
"created": {
"date-parts": [
[
2021,
4,
21
]
],
"date-time": "2021-04-21T22:40:54Z",
"timestamp": 1619044854000
},
"deposited": {
"date-parts": [
[
2023,
4,
15
]
],
"date-time": "2023-04-15T09:17:15Z",
"timestamp": 1681550235000
},
"indexed": {
"date-parts": [
[
2024,
1,
23
]
],
"date-time": "2024-01-23T18:05:12Z",
"timestamp": 1706033112952
},
"is-referenced-by-count": 28,
"issued": {
"date-parts": [
[
2021,
8
]
]
},
"language": "en",
"license": [
{
"URL": "https://www.elsevier.com/tdm/userlicense/1.0/",
"content-version": "tdm",
"delay-in-days": 0,
"start": {
"date-parts": [
[
2021,
8,
1
]
],
"date-time": "2021-08-01T00:00:00Z",
"timestamp": 1627776000000
}
},
{
"URL": "https://doi.org/10.15223/policy-017",
"content-version": "stm-asf",
"delay-in-days": 0,
"start": {
"date-parts": [
[
2021,
8,
1
]
],
"date-time": "2021-08-01T00:00:00Z",
"timestamp": 1627776000000
}
},
{
"URL": "https://doi.org/10.15223/policy-037",
"content-version": "stm-asf",
"delay-in-days": 0,
"start": {
"date-parts": [
[
2021,
8,
1
]
],
"date-time": "2021-08-01T00:00:00Z",
"timestamp": 1627776000000
}
},
{
"URL": "https://doi.org/10.15223/policy-012",
"content-version": "stm-asf",
"delay-in-days": 0,
"start": {
"date-parts": [
[
2021,
8,
1
]
],
"date-time": "2021-08-01T00:00:00Z",
"timestamp": 1627776000000
}
},
{
"URL": "https://doi.org/10.15223/policy-029",
"content-version": "stm-asf",
"delay-in-days": 0,
"start": {
"date-parts": [
[
2021,
8,
1
]
],
"date-time": "2021-08-01T00:00:00Z",
"timestamp": 1627776000000
}
},
{
"URL": "https://doi.org/10.15223/policy-004",
"content-version": "stm-asf",
"delay-in-days": 0,
"start": {
"date-parts": [
[
2021,
8,
1
]
],
"date-time": "2021-08-01T00:00:00Z",
"timestamp": 1627776000000
}
}
],
"link": [
{
"URL": "https://api.elsevier.com/content/article/PII:S1567576921003386?httpAccept=text/xml",
"content-type": "text/xml",
"content-version": "vor",
"intended-application": "text-mining"
},
{
"URL": "https://api.elsevier.com/content/article/PII:S1567576921003386?httpAccept=text/plain",
"content-type": "text/plain",
"content-version": "vor",
"intended-application": "text-mining"
}
],
"member": "78",
"original-title": [],
"page": "107702",
"prefix": "10.1016",
"published": {
"date-parts": [
[
2021,
8
]
]
},
"published-print": {
"date-parts": [
[
2021,
8
]
]
},
"publisher": "Elsevier BV",
"reference": [
{
"DOI": "10.1056/NEJMoa2001316",
"article-title": "Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia",
"author": "Li",
"doi-asserted-by": "crossref",
"first-page": "1199",
"issue": "13",
"journal-title": "New Engl. J. Med.",
"key": "10.1016/j.intimp.2021.107702_b0005",
"volume": "382",
"year": "2020"
},
{
"key": "10.1016/j.intimp.2021.107702_b0010",
"unstructured": "http://2019ncov.chinacdc.cn/2019-nCoV/global.html (accessed December 24, 2020)."
},
{
"key": "10.1016/j.intimp.2021.107702_b0015",
"unstructured": "Diagnosis and treatment protocol for novel coronavirus pneumonia (seventh edition). http://www.gov.cn/zhengce/zhengceku/2020-03/04/5486705/files/ae61004f930d47598711a0d4cbf874a9.pdf (accessed July 10, 2020)."
},
{
"DOI": "10.1001/jama.2020.2783",
"doi-asserted-by": "crossref",
"key": "10.1016/j.intimp.2021.107702_b0020",
"unstructured": "L Lan, D Xu, G Ye, C Xia, S Wang, Y Li et al. Positive RT-PCR Test Results in Patients Recovered From COVID-19. JAMA. 2020 Apr 21;323(15):1502-1503."
},
{
"DOI": "10.1016/S1473-3099(20)30433-3",
"article-title": "Assessment of patients who tested positive for COVID-19 after recovery",
"author": "Mei",
"doi-asserted-by": "crossref",
"first-page": "1004",
"issue": "9",
"journal-title": "Lancet Infect. Dis.",
"key": "10.1016/j.intimp.2021.107702_b0025",
"volume": "20",
"year": "2020"
},
{
"DOI": "10.1016/j.tmaid.2020.101619",
"article-title": "Positive result of Sars-Cov-2 in sputum from a cured patient with COVID-19",
"author": "Qu",
"doi-asserted-by": "crossref",
"journal-title": "Travel Med. Infect. Dis.",
"key": "10.1016/j.intimp.2021.107702_b0030",
"volume": "34",
"year": "2020"
},
{
"DOI": "10.1097/CM9.0000000000000774",
"article-title": "Persistence and clearance of viral RNA in 2019 novel coronavirus disease rehabilitation patients",
"author": "Ling",
"doi-asserted-by": "crossref",
"first-page": "1039",
"issue": "9",
"journal-title": "Chin. Med. J.",
"key": "10.1016/j.intimp.2021.107702_b0035",
"volume": "133",
"year": "2020"
},
{
"DOI": "10.1101/2020.03.26.20044222",
"doi-asserted-by": "crossref",
"key": "10.1016/j.intimp.2021.107702_b0040",
"unstructured": "J An, X Liao, T Xiao, S Qian, J Yuan, H Ye, et al., Clinical characteristics of the recovered COVID-19 patients with re-detectable positive RNA test, medRxiv (2020) 2020.03.26.20044222."
},
{
"DOI": "10.1093/jac/dkaa171",
"article-title": "an antiviral for COVID-19?",
"author": "Coomes",
"doi-asserted-by": "crossref",
"first-page": "2013",
"issue": "7",
"journal-title": "J. Antimicrobial Chemotherapy",
"key": "10.1016/j.intimp.2021.107702_b0045",
"volume": "75",
"year": "2020"
},
{
"DOI": "10.1093/cid/ciw571",
"article-title": "Clinical and Virological Characteristics of Ebola Virus Disease Patients Treated With Favipiravir (T-705)-Sierra Leone, 2014",
"author": "Bai",
"doi-asserted-by": "crossref",
"first-page": "1288",
"issue": "10",
"journal-title": "Clin. Infect. Dis.",
"key": "10.1016/j.intimp.2021.107702_b0050",
"volume": "63",
"year": "2016"
},
{
"DOI": "10.1038/s41422-020-0282-0",
"article-title": "Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro",
"author": "Wang",
"doi-asserted-by": "crossref",
"first-page": "269",
"issue": "3",
"journal-title": "Cell Res.",
"key": "10.1016/j.intimp.2021.107702_b0055",
"volume": "30",
"year": "2020"
},
{
"DOI": "10.1016/j.eng.2020.03.007",
"article-title": "Experimental Treatment with Favipiravir for COVID-19: An Open-Label Control Study",
"author": "Cai",
"doi-asserted-by": "crossref",
"journal-title": "Engineering",
"key": "10.1016/j.intimp.2021.107702_b0060",
"year": "2020"
},
{
"DOI": "10.1186/s13063-020-04430-y",
"author": "Li",
"doi-asserted-by": "crossref",
"first-page": "488",
"issue": "1",
"journal-title": "Trials",
"key": "10.1016/j.intimp.2021.107702_b0065",
"volume": "21",
"year": "2020"
},
{
"DOI": "10.1016/S0140-6736(20)31042-4",
"article-title": "Triple combination of interferon beta-1b, lopinavir-ritonavir, and ribavirin in the treatment of patients admitted to hospital with COVID-19: an open-label, randomised, phase 2 trial",
"author": "Hung",
"doi-asserted-by": "crossref",
"first-page": "1695",
"issue": "10238",
"journal-title": "Lancet",
"key": "10.1016/j.intimp.2021.107702_b0070",
"volume": "395",
"year": "2020"
},
{
"DOI": "10.1016/S0140-6736(20)30744-3",
"article-title": "Fangcang shelter hospitals: a novel concept for responding to public health emergencies",
"author": "Chen",
"doi-asserted-by": "crossref",
"first-page": "1305",
"issue": "10232",
"journal-title": "Lancet",
"key": "10.1016/j.intimp.2021.107702_b0075",
"volume": "395",
"year": "2020"
},
{
"DOI": "10.1016/j.mayocp.2020.04.027",
"article-title": "Treatment Considerations for COVID-19: A Critical Review of the Evidence (or Lack Thereof)",
"author": "Vijayvargiya",
"doi-asserted-by": "crossref",
"first-page": "1454",
"issue": "7",
"journal-title": "Mayo Clin. Proc.",
"key": "10.1016/j.intimp.2021.107702_b0080",
"volume": "95",
"year": "2020"
},
{
"DOI": "10.1056/NEJMoa2012410",
"article-title": "Observational Study of Hydroxychloroquine in Hospitalized Patients with Covid-19",
"author": "Geleris",
"doi-asserted-by": "crossref",
"first-page": "2411",
"issue": "25",
"journal-title": "New Engl. J. Med.",
"key": "10.1016/j.intimp.2021.107702_b0085",
"volume": "382",
"year": "2020"
},
{
"article-title": "Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: open label, randomised controlled trial",
"author": "Tang",
"journal-title": "BMJ (Clinical research ed.)",
"key": "10.1016/j.intimp.2021.107702_b0090",
"volume": "369",
"year": "2020"
},
{
"DOI": "10.1016/S0140-6736(20)31022-9",
"article-title": "Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial",
"author": "Wang",
"doi-asserted-by": "crossref",
"first-page": "1569",
"issue": "10236",
"journal-title": "Lancet (London, England)",
"key": "10.1016/j.intimp.2021.107702_b0095",
"volume": "395",
"year": "2020"
},
{
"DOI": "10.1056/NEJMoa2007764",
"article-title": "Remdesivir for the Treatment of Covid-19 - Preliminary Report",
"author": "Beigel",
"doi-asserted-by": "crossref",
"journal-title": "New Engl. J. Med.",
"key": "10.1016/j.intimp.2021.107702_b0100",
"year": "2020"
},
{
"DOI": "10.1056/NEJMoa2001282",
"article-title": "A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19",
"author": "Cao",
"doi-asserted-by": "crossref",
"first-page": "1787",
"issue": "19",
"journal-title": "N. Engl. J. Med.",
"key": "10.1016/j.intimp.2021.107702_b0105",
"volume": "382",
"year": "2020"
},
{
"DOI": "10.1080/22221751.2020.1827983",
"article-title": "Prolonged presence of viral nucleic acid in clinically recovered COVID-19 patients was not associated with effective infectiousness",
"author": "Hong",
"doi-asserted-by": "crossref",
"first-page": "2315",
"issue": "1",
"journal-title": "Emerg. Microbes. Infect.",
"key": "10.1016/j.intimp.2021.107702_b0110",
"volume": "9",
"year": "2020"
},
{
"DOI": "10.1080/22221751.2020.1837018",
"article-title": "Viral RNA level, serum antibody responses, and transmission risk in recovered COVID-19 patients with recurrent positive SARS-CoV-2 RNA test results: a population-based observational cohort study",
"author": "Yang",
"doi-asserted-by": "crossref",
"first-page": "2368",
"issue": "1",
"journal-title": "Emerg. Microbes. Infect.",
"key": "10.1016/j.intimp.2021.107702_b0115",
"volume": "9",
"year": "2020"
},
{
"DOI": "10.1038/s41422-020-0318-5",
"article-title": "Pathological evidence for residual SARS-CoV-2 in pulmonary tissues of a ready-for-discharge patient",
"author": "Yao",
"doi-asserted-by": "crossref",
"first-page": "541",
"issue": "6",
"journal-title": "Cell Res",
"key": "10.1016/j.intimp.2021.107702_b0120",
"volume": "30",
"year": "2020"
},
{
"DOI": "10.3389/fimmu.2020.00827",
"article-title": "Reduction and Functional Exhaustion of T Cells in Patients With Coronavirus Disease 2019 (COVID-19)",
"author": "Diao",
"doi-asserted-by": "crossref",
"first-page": "827",
"journal-title": "Front. Immunol.",
"key": "10.1016/j.intimp.2021.107702_b0125",
"volume": "11",
"year": "2020"
},
{
"DOI": "10.1016/j.cell.2020.06.040",
"article-title": "Making sense of mutation: what D614G means for the COVID-19 pandemic remains unclear",
"author": "Grubaugh",
"doi-asserted-by": "crossref",
"journal-title": "Cell",
"key": "10.1016/j.intimp.2021.107702_b0130",
"year": "2020"
},
{
"DOI": "10.1016/j.cell.2020.06.043",
"article-title": "Tracking changes in SARS-CoV-2 Spike: evidence that D614G increases infectivity of the COVID-19 virus",
"author": "Korber",
"doi-asserted-by": "crossref",
"journal-title": "Cell",
"key": "10.1016/j.intimp.2021.107702_b0135",
"year": "2020"
},
{
"DOI": "10.1093/nsr/nwaa036",
"article-title": "On the origin and continuing evolution of SARS-CoV-2",
"author": "Tang",
"doi-asserted-by": "crossref",
"first-page": "1012",
"issue": "6",
"journal-title": "Natl. Sci. Rev.",
"key": "10.1016/j.intimp.2021.107702_b0140",
"volume": "7",
"year": "2020"
},
{
"article-title": "Cause analysis and treatment strategies of “recurrence” with novel coronavirus pneumonia (COVID-19) patients after discharge from hospital (in Chinese)",
"author": "Zhou",
"first-page": "281",
"issue": "4",
"journal-title": "Chin. J. Tuberculosis Respiratory Dis.",
"key": "10.1016/j.intimp.2021.107702_b0145",
"volume": "43",
"year": "2020"
},
{
"key": "10.1016/j.intimp.2021.107702_b0150",
"unstructured": "The intersection of COVID-19 and mental health. https://www.sciencedirect.com/science/article/pii/S1473309920307970 (accessed February 14, 2021)."
},
{
"DOI": "10.1016/S2215-0366(20)30491-0",
"article-title": "The mental health impact of the COVID-19 pandemic on people with and without depressive, anxiety, or obsessive-compulsive disorders: a longitudinal study of three Dutch case-control cohorts",
"author": "Pan",
"doi-asserted-by": "crossref",
"first-page": "121",
"issue": "2",
"journal-title": "Lancet Psychiatry",
"key": "10.1016/j.intimp.2021.107702_b0155",
"volume": "8",
"year": "2021"
},
{
"DOI": "10.1016/j.bbi.2020.06.002",
"article-title": "Mental health status of medical staff in emergency departments during the Coronavirus disease 2019 epidemic in China",
"author": "Song",
"doi-asserted-by": "crossref",
"first-page": "60",
"journal-title": "Brain Behav. Immun.",
"key": "10.1016/j.intimp.2021.107702_b0160",
"volume": "88",
"year": "2020"
},
{
"key": "10.1016/j.intimp.2021.107702_b0165",
"unstructured": "https://news.sina.com.cn/c/2020-03-30/doc-iimxyqwa4112916.shtml (accessed February 24, 2021)."
}
],
"reference-count": 33,
"references-count": 33,
"relation": {},
"resource": {
"primary": {
"URL": "https://linkinghub.elsevier.com/retrieve/pii/S1567576921003386"
}
},
"score": 1,
"short-title": [],
"source": "Crossref",
"subject": [
"Pharmacology",
"Immunology",
"Immunology and Allergy"
],
"subtitle": [],
"title": "Favipiravir in the treatment of patients with SARS-CoV-2 RNA recurrent positive after discharge: A multicenter, open-label, randomized trial",
"type": "journal-article",
"update-policy": "http://dx.doi.org/10.1016/elsevier_cm_policy",
"volume": "97"
}
Late treatment
is less effective
is less effective
