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

Asaf Biber; Geva Harmelin; Dana Lev; Li Ram; Amit Shaham; Ital Nemet; Limor Kliker; Oran Erster; Michal Mandelboim; Eli Schwartz

doi:10.1016/j.ijid.2022.07.003

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

Asaf Biber
, Geva Harmelin
, Dana Lev
, Li Ram
, Amit Shaham
, Ital Nemet
, Limor Kliker
, Oran Erster
, Michal Mandelboim
, Eli Schwartz

Sheba Medical Center at Tel Hashomer
Tel Aviv University
Ministry of Health, Israel

Research output: Contribution to journal › Article › peer-review

21 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	733-740
Number of pages	8
Journal	International Journal of Infectious Diseases
Volume	122
DOIs	https://doi.org/10.1016/j.ijid.2022.07.003
State	Published - Sep 2022
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2022

Funding

The authors have no competing interests to declare. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. We would like to thank Super-Pharm Professional for donating the drug and the placebo pills, Ms. Liraz Olmer for statistical analysis support, Ms. Rivka Goldis for administration aids, Dr. Emiliano Cohen for graph producing, and Mr. Nadav Cain for his logistic support. Finally, we would like to thank the Directorate of Defense Research and Development at Israel's Ministry of Defense and Home Front Command staff, who helped us access the dedicated COVID-19 isolation hotels; without their support, the study could not have been performed. Conceptualization: ES; Data curation: ES, AB, MM; Formal analysis: ES, AB, MM, OE; Investigation: AB, MM, GH, DL, LR, AS, IN, LK, OE, ES; Methodology: ES, AB, MM, OE; Supervision: ES, AB; Writing - original draft: ES, AB, DL; Writing - review & editing: all authors contributed, reviewed, and approved the last draft.

Funders
Directorate of Defense Research and Development at Israel's Ministry of Defense
Home Front Command staff

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

COVID-19
Infectivity duration
Ivermectin
SARS-CoV-2
Viral cultures

Access to Document

10.1016/j.ijid.2022.07.003

Cite this

Biber, A., Harmelin, G., Lev, D., Ram, L., Shaham, A., Nemet, I., Kliker, L., Erster, O., Mandelboim, M., & Schwartz, E. (2022). 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. International Journal of Infectious Diseases, 122, 733-740. https://doi.org/10.1016/j.ijid.2022.07.003

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title = "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",

abstract = "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.",

keywords = "COVID-19, Infectivity duration, Ivermectin, SARS-CoV-2, Viral cultures",

author = "Asaf Biber and Geva Harmelin and Dana Lev and Li Ram and Amit Shaham and Ital Nemet and Limor Kliker and Oran Erster and Michal Mandelboim and Eli Schwartz",

note = "Publisher Copyright: {\textcopyright} 2022",

year = "2022",

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doi = "10.1016/j.ijid.2022.07.003",

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Biber, A, Harmelin, G, Lev, D, Ram, L, Shaham, A, Nemet, I, Kliker, L, Erster, O, Mandelboim, M & Schwartz, E 2022, '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', International Journal of Infectious Diseases, vol. 122, pp. 733-740. https://doi.org/10.1016/j.ijid.2022.07.003

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. / Biber, Asaf; Harmelin, Geva; Lev, Dana et al.
In: International Journal of Infectious Diseases, Vol. 122, 09.2022, p. 733-740.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - 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

AU - Biber, Asaf

AU - Harmelin, Geva

AU - Lev, Dana

AU - Ram, Li

AU - Shaham, Amit

AU - Nemet, Ital

AU - Kliker, Limor

AU - Erster, Oran

AU - Mandelboim, Michal

AU - Schwartz, Eli

PY - 2022/9

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N2 - 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.

AB - 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.

KW - COVID-19

KW - Infectivity duration

KW - Ivermectin

KW - SARS-CoV-2

KW - Viral cultures

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ER -

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

Abstract

Bibliographical note

Funding

UN SDGs

Keywords

Access to Document

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