The effect of ivermectin on the viral load and culture viability in early treatment of nonhospitalized patients with mild COVID-19-a double-blind, randomized placebo-controlled trial

被引:13
作者
Biber, Asaf [1 ,2 ]
Harmelin, Geva [3 ]
Lev, Dana [1 ,2 ]
Ram, Li [3 ]
Shaham, Amit [3 ]
Nemet, Ital [4 ]
Kliker, Limor [4 ]
Erster, Oran [4 ]
Mandelboim, Michal [2 ,4 ]
Schwartz, Eli [1 ,2 ]
机构
[1] Sheba Med Ctr, Ctr Geog Med & Trop Dis, Ramat Gan, Israel
[2] Tel Aviv Univ, Sackler Fac Med, Tel Aviv, Israel
[3] Sheba Med Ctr, Emergency Med, Ramat Gan, Israel
[4] Minist Hlth, Cent Virol Lab, Ramat Gan, Israel
关键词
SARS-CoV-2; Viral cultures; Infectivity duration; Ivermectin; COVID-19; NUCLEAR IMPORT; INHIBITOR;
D O I
10.1016/j.ijid.2022.07.003
中图分类号
R51 [传染病];
学科分类号
100401 ;
摘要
Objectives: Ivermectin, an antiparasitic agent, also has antiviral properties. In this study, we aimed to assess whether ivermectin has anti-SARS-CoV-2 activity. Methods: In this double-blinded trial, we compared patients receiving ivermectin for 3 days versus placebo in nonhospitalized adult patients with COVID-19. A reverse transcriptase-polymerase chain reaction from a nasopharyngeal swab was obtained at recruitment and every 2 days for at least 6 days. The primary endpoint was a reduction of viral load on the sixth day as reflected by cycle threshold level >30 (noninfectious level). The primary outcome was supported by the determination of viral-culture viability. Results: Of 867 patients screened, 89 were ultimately evaluated per-protocol (47 ivermectin and 42 placeboes). On day 6, the odds ratio (OR) was 2.62 (95% confidence interval [CI]: 1.09-6.31) in the ivermectin arm, reaching the endpoint. In a multivariable logistic regression model, the odds of a negative test on day 6 were 2.28 times higher in the ivermectin group but reached significance only on day 8 (OR 3.70; 95% CI: 1.19-11.49, P = 0.02). Culture viability on days 2 to 6 was positive in 13.0% (3/23) of ivermectin samples versus 48.2% (14/29) in the placebo group (P = 0.008). Conclusion: There were lower viral loads and less viable cultures in the ivermectin group, which shows its anti-SARS-CoV-2 activity. It could reduce transmission in these patients and encourage further studies with this drug. (c) 2022 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
引用
收藏
页码:733 / 740
页数:8
相关论文
共 32 条
  • [1] SARS-CoV-2 RNA identification in nasopharyngeal swabs: issues in pre-analytics
    Basso, Daniela
    Aita, Ada
    Navaglia, Filippo
    Franchin, Elisa
    Fioretto, Paola
    Moz, Stefania
    Bozzato, Dania
    Zambon, Carlo-Federico
    Martin, Barbara
    Dal Pra, Chiara
    Crisanti, Andrea
    Plebani, Mario
    [J]. CLINICAL CHEMISTRY AND LABORATORY MEDICINE, 2020, 58 (09) : 1579 - 1586
  • [2] Remdesivir significantly reduces SARS-CoV-2 viral load on nasopharyngeal swabs in hospitalized patients with COVID-19: A retrospective case-control study
    Biancofiore, Annalucia
    Mirijello, Antonio
    Puteo, Maria A.
    Di Viesti, Maria P.
    Labonia, Maria
    Copetti, Massimiliano
    De Cosmo, Salvatore
    Lombardi, Renato
    [J]. JOURNAL OF MEDICAL VIROLOGY, 2022, 94 (05) : 2284 - 2289
  • [3] Snapshot PCR surveillance for SARS-CoV-2 in hospital staff in England
    Brown, Colin S.
    Clare, Kathryn
    Chand, Meera
    Andrews, Julie
    Auckland, Cressida
    Beshir, Sarah
    Choudhry, Saher
    Davies, Kerrie
    Freeman, Jane
    Gallini, Andrew
    Moores, Rachel
    Patel, Trupti
    Poznalska, Gosia
    Rodger, Alison
    Roberts, Stella
    Rooney, Christopher
    Wilcox, Mark
    Warren, Simon
    Ellis, Joanna
    Gopal, Robin
    Dunning, Jake
    Zambon, Maria
    Hopkins, Susan
    [J]. JOURNAL OF INFECTION, 2020, 81 (03) : 427 - 434
  • [4] Ivermectin for Prevention and Treatment of COVID-19 Infection: A Systematic Review, Meta-analysis, and Trial Sequential Analysis to Inform Clinical Guidelines
    Bryant, Andrew
    Lawrie, Theresa A.
    Dowswell, Therese
    Fordham, Edmund J.
    Mitchell, Scott
    Hill, Sarah R.
    Tham, Tony C.
    [J]. AMERICAN JOURNAL OF THERAPEUTICS, 2021, 28 (04) : E434 - E460
  • [5] Predicting Infectious Severe Acute Respiratory Syndrome Coronavirus 2 From Diagnostic Samples
    Bullard, Jared
    Dust, Kerry
    Funk, Duane
    Strong, James E.
    Alexander, David
    Garnett, Lauren
    Boodman, Carl
    Bello, Alexander
    Hedley, Adam
    Schiffman, Zachary
    Doan, Kaylie
    Bastien, Nathalie
    Li, Yan
    Van Caeseele, Paul G.
    Poliquin, Guillaume
    [J]. CLINICAL INFECTIOUS DISEASES, 2020, 71 (10) : 2663 - 2666
  • [6] The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro
    Caly, Leon
    Druce, Julian D.
    Catton, Mike G.
    Jans, David A.
    Wagstaff, Kylie M.
    [J]. ANTIVIRAL RESEARCH, 2020, 178
  • [7] Nuclear trafficking of proteins from RNA viruses: Potential target for antivirals?
    Caly, Leon
    Wagstaff, Kylie M.
    Jans, David A.
    [J]. ANTIVIRAL RESEARCH, 2012, 95 (03) : 202 - 206
  • [8] Carroll A, 2021, EUROSURVEILLANCE, P26
  • [9] Exploring the binding efficacy of ivermectin against the key proteins of SARS-CoV-2 pathogenesis: an in silico approach
    Choudhury, Abhigyan
    Das, Nabarun C.
    Patra, Ritwik
    Bhattacharya, Manojit
    Ghosh, Pratik
    Patra, Bidhan C.
    Mukherjee, Suprabhat
    [J]. FUTURE VIROLOGY, 2021, 16 (04) : 277 - 291
  • [10] Molecular Docking Reveals Ivermectin and Remdesivir as Potential Repurposed Drugs Against SARS-CoV-2
    Eweas, Ahmad F.
    Alhossary, Amr A.
    Abdel-Moneim, Ahmed S.
    [J]. FRONTIERS IN MICROBIOLOGY, 2021, 11