ArticlePDF Available

Ivermectin for COVID-19: Addressing Potential Bias and Medical Fraud

Authors:
Andrew Hill at University of Liverpool
Andrew Hill
Manya Mirchandani
Manya Mirchandani
Manya Mirchandani
  • This person is not on ResearchGate, or hasn't claimed this research yet.
Victoria Pilkington at St George's, University of London
Victoria Pilkington
Download full-text PDF
Read full-text
Download citation

Abstract

Ivermectin has become a controversial potential medicine for COVID-19. Some early studies suggested clinical benefits in treatment of infection. However, the body of evidence includes studies of varying quality. Furthermore, some trials have now been identified as potentially fraudulent. We present a sub-group meta-analysis, to assess the effects of stratifying by trial quality on the overall results. The stratification is based on the Cochrane Risk of Bias measures (RoB 2) and raw data analysis where possible. The results suggest that the significant effect of ivermectin on survival was dependent on largely poor-quality studies. According to the potentially fraudulent study (RR=0.08, 95% CI=0.02,0.35), ivermectin improved survival approximately 12 times more in comparison to low-risk studies (RR=0.96, 95% CI=0.56,1.66). This highlights the need for rigorous quality assessments, authors to share patient-level data and efforts to avoid publication bias for registered studies. These steps are vital to facilitate accurate conclusions on clinical treatments.
Available via license: CC BY-NC-ND 4.0
Content may be subject to copyright.
Accepted Manuscript
Ivermectin for COVID-19: addressing potential bias and medical
1
fraud
2
3
Andrew Hill1, Manya Mirchandani2, Victoria Pilkington3
4
5
1. Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool, L7
6
3NY, UK
7
2. Faculty of Medicine, Imperial College London, UK
8
3. Oxford University Clinical Academic Graduate School, University of Oxford, UK
9
10
11
Corresponding author:
12
Manya Mirchandani
13
Faculty of Medicine
14
Imperial College London
15
United Kingdom
16
Email: manya.mirchandani20@imperial.ac.uk
17
18
Funding: The Rainwater Charitable Foundation
19
20
Potential Conflicts of Interest: None of the authors has declared a conflict of interest
21
22
Patient Consent Statement: All the clinical trials included in the meta-analysis were
23
approved by local ethics committees and all patients gave informed consent.
24
25
26
27
28
Downloaded from https://academic.oup.com/ofid/advance-article/doi/10.1093/ofid/ofab645/6509922 by guest on 18 January 2022
Accepted Manuscript
Abstract
29
30
Ivermectin has become a controversial potential medicine for COVID-19. Some early studies
31
suggested clinical benefits in treatment of infection. However, the body of evidence includes
32
studies of varying quality. Furthermore, some trials have now been identified as potentially
33
fraudulent.
34
35
We present a sub-group meta-analysis, to assess the effects of stratifying by trial quality on
36
the overall results. The stratification is based on the Cochrane Risk of Bias measures (RoB
37
2) and raw data analysis where possible.
38
39
The results suggest that the significant effect of ivermectin on survival was dependent on
40
largely poor-quality studies. According to the potentially fraudulent study (RR=0.08, 95%
41
CI=0.02,0.35), ivermectin improved survival approximately 12 times more in comparison to
42
low-risk studies (RR=0.96, 95% CI=0.56,1.66). This highlights the need for rigorous quality
43
assessments, authors to share patient-level data and efforts to avoid publication bias for
44
registered studies. These steps are vital to facilitate accurate conclusions on clinical
45
treatments.
46
Downloaded from https://academic.oup.com/ofid/advance-article/doi/10.1093/ofid/ofab645/6509922 by guest on 18 January 2022
Accepted Manuscript
In June 2020 ivermectin, an FDA approved anti-parasitic drug, was shown to have anti-viral
47
effects against SARS-CoV-2 in-vitro1. Following this, approximately 86 clinical trials
48
investigating ivermectin for COVID-19 have been registered globally. In late 2020, clinical
49
trials began reporting very compelling clinical benefits for ivermectin in the treatment of
50
COVID-19. From late 2020 onwards, multiple groups produced meta-analyses which
51
reported that ivermectin had a significant effect on survival, hospitalisations, clinical recovery
52
and viral clearance2, 3. Our meta-analysis was first presented in January 2021 and published
53
in July 20214. It suggested that ivermectin resulted in a significant 56% improvement in
54
survival, favourable clinical recovery, and reduced hospitalisations. Such optimistic results
55
from multiple meta-analyses have escalated public interest in using ivermectin for the
56
treatment and prevention of COVID-19, despite the WHO only recommending its use within
57
clinical trials5, 6.
58
59
However, as with all meta-analyses, a key limitation is the quality and completeness of the
60
available evidence. During our original assessment of studies, standardised Cochrane Risk
61
of Bias measures (RoB 2) had classified several studies as „high risk of bias‟7. A study by
62
Niaee et al from Iran which reported a randomised methodology, was found to have
63
significant differences in baseline characteristics across treatment arms8. This suggested
64
that the participants were not randomised appropriately, which could bias the outcomes.
65
Secondly, a study by Okumus et al from Turkey did not provide any information on allocation
66
concealment and it was unclear if the participants or investigators were blinded, which risks
67
introducing observation bias9. Lastly, a study by Hashim et al from Iraq provided insufficient
68
details on the randomisation process, lack of clarity on participants who were analysed and
69
involved unblinded assessment of a subjective outcome10.
70
71
Furthermore, some studies were then identified to be potentially fraudulent. For example, on
72
15th July 2021, a study by Elgazzar et al from Egypt was retracted from pre-print server
73
Research Square due to “ethical concerns”11. It has been reported that the data for
74
approximately 79 participants were duplicates, some deaths were recorded on dates before
75
the trial had started and instances of plagiarism were identified in the text12. Similarly, a
76
study conducted in Lebanon by Raad et al was also identified to have duplicate data for
77
multiple participants when the patient-level database was analysed in September 202113.
78
Before these inconsistencies were identified, the Elgazzar and Raad studies had been
79
included in multiple meta-analyses which suggested significant benefits for ivermectin in the
80
treatment of COVID-192, 3. In our original meta-analysis, the Raad study accounted for
81
Downloaded from https://academic.oup.com/ofid/advance-article/doi/10.1093/ofid/ofab645/6509922 by guest on 18 January 2022
Accepted Manuscript
11.8% of the effect of ivermectin on hospitalisation and the Elgazzar study accounted for
82
12.6% of the effect of ivermectin on survival4.
83
These instances suggest that the data available to the support the use of ivermectin for
84
COVID-19 are not reliable. In July 2021, after the potentially fraudulent studies were
85
identified, we retracted our published meta-analysis and began working on an updated
86
analysis, assessing the effects of stratifying by trial quality on the overall results. Clinical
87
trials evaluating ivermectin for the treatment of COVID-19 had been identified by systematic
88
search of 8 databases. An in-depth evaluation of study quality was conducted, in addition to
89
the standard Cochrane risk of bias tool (RoB 2) and CONSORT checklist7. Firstly, we
90
evaluated trials based on the effectiveness of their randomisation process by comparing
91
baseline characteristics across treatment arms using the chi-square test. Secondly,
92
randomisation dates were checked to ensure patients were randomised into the treatment
93
arms on similar dates. Thirdly, checks were conducted to evaluate if recruitment to treatment
94
arms was balanced at each investigational centre. Furthermore, we analysed patient-level
95
databases, where available, to check for any evidence of duplicate participants, unexpected
96
homogeneity or heterogeneity. From this, a meta-analysis was conducted with sub-groups of
97
clinical trials at different risk of bias levels.
98
99
Looking at the key survival outcome, the analysis includes 12 studies with a total of 2628
100
participants4 (Table 1). This included 4 studies at a low risk of bias, 4 with some concerns, 3
101
at a high risk of bias and 1 potentially fraudulent study. The analysis demonstrates that on
102
including all 12 studies, ivermectin results in a significant 51% increase in survival (p=0.01,
103
95% CI = 0.28-0.86) (Figure 1, Supplementary Figure 1). On excluding the potentially
104
fraudulent Elgazzar study, ivermectin results in a borderline significant 38% increase in
105
survival (p=0.05, 95% CI = 0.39-0.99) (Figure 1, Supplementary Figure 2). On excluding the
106
high risk of bias studies, ivermectin results in a non-significant 10% increase in survival
107
(p=0.66, 95% CI = 0.57-1.42) (Figure 1, Supplementary Figure 3). Lastly, on excluding
108
studies with some concerns of bias, ivermectin results in a non-significant 4% increase in
109
survival (p=0.90, 95% CI = 0.56-1.66) (Figure 1, Supplementary Figure 4). These
110
observations demonstrate that the significant effect of ivermectin on survival was dependent
111
on the inclusion of studies with a high risk of bias or potential medical fraud.
112
113
There are added challenges with clinical trials investigating COVID-19 treatments. In a rapid
114
response to COVID-19, many small-scale studies have been conducted globally for potential
115
agents. However, not all trials have reported findings. An example is a trial for Nitazoxanide
116
in Brazil with 600 participants which was completed in October 2020 but has not reported
117
Downloaded from https://academic.oup.com/ofid/advance-article/doi/10.1093/ofid/ofab645/6509922 by guest on 18 January 2022
Accepted Manuscript
any results yet14. Publication bias impacts meta-analyses, with positive and significant
118
results more likely to be reported. Therefore, we believe that by including publication bias, it
119
is even less likely that ivermectin will show significant benefits for COVID-19 treatment.
120
Some non-randomised trials may also be over-interpreted. For example, in a non-
121
randomised retrospective cohort study, remdesivir demonstrated an improvement in clinical
122
recovery and reduced mortality risk by 62%15. However, when evaluated in the WHO‟s
123
randomised placebo-controlled SOLIDARITY trial, remdesivir had little to no effect on
124
mortality16. Any initial promising findings from a small number of sources need to be
125
interpreted with caution, studied further and considered within the wider body of evidence.
126
127
The results from this analysis highlight the need for rigorous quality assessments when
128
evaluating clinical trials of drugs for COVID-19. Existing and widely used risk of bias
129
assessment tools are not enough. These tools provide a systematic framework for identifying
130
potential key sources of bias in a trial‟s internal methodology but work on the fundamental
131
assumption that a published study is reporting accurate and complete findings. They allow
132
reviewers to make judgements on the assumption that basic standard procedure is followed,
133
the data are real, and that no information is being intentionally hidden.
134
135
With cases of potential medical fraud now identified, it is essential that access to patient-
136
level databases is provided. If authors fail to provide these data, the study should be
137
considered with a higher index of suspicion. Additionally, it should be mandatory that all
138
registered trials report their findings. We understand that these are substantial changes to
139
established procedures. However, the failure to recognise the potentially fraudulent studies,
140
which led to multiple meta-analyses suggesting significant benefits of ivermectin for COVID-
141
19, indicates that the tools currently used to evaluate the quality of clinical trials are
142
insufficient. These events warrant our stringent recommendations.
143
144
145
Acknowledgements
146
We would like to thank Gideon Meyerowitz-Katz, Kyle A. Sheldrick and Jack M. Lawrence for
147
their help with the quality assessments.
148
Downloaded from https://academic.oup.com/ofid/advance-article/doi/10.1093/ofid/ofab645/6509922 by guest on 18 January 2022
Accepted Manuscript
REFERENCES
149
150
1) Caly, L., Druce, J., Catton, M., Jans, D., & Wagstaff, K. (2020). The FDA-approved drug
151
ivermectin inhibits the replication of SARS-CoV-2 in vitro. Antiviral Research, 178, 104787.
152
doi: 10.1016/j.antiviral.2020.104787
153
154
2) Bryant A, Lawrie TA, Dowswell T, Fordham EJ, Mitchell S, Hill SR, et al. Ivermectin for
155
Prevention and Treatment of COVID-19 Infection: A Systematic Review, Meta-analysis, and
156
Trial Sequential Analysis to Inform Clinical Guidelines. American Journal of Therapeutics.
157
2021;28(4).
158
159
3) Kory P, Meduri GU, Varon J, Iglesias J, Marik PE. Review of the Emerging Evidence
160
Demonstrating the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19.
161
American Journal of Therapeutics. 2021;28(3).
162
163
4) Hill, A., Garratt, A., Levi, J., Falconer, J., Ellis, L., & McCann, K. et al. (2021). Meta-
164
analysis of randomized trials of ivermectin to treat SARS-CoV-2 infection. Open Forum
165
Infectious Diseases. doi: 10.1093/ofid/ofab358
166
167
5) Desperation, misinformation: how the ivermectin craze spread across the world. (2021).
168
Retrieved 15 October 2021, from
169
https://www.theguardian.com/world/2021/sep/24/ivermectin-covid-peru-misinformation
170
171
6) WHO. Therapeutics and COVID-19: Living Guideline 2021. Retrieved 13 October 2021.
172
Available from: https://www.who.int/publications/i/item/WHO-2019-nCoV-therapeutics-
173
2021.2.
174
175
7) Sterne JAC, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I, Cates CJ, Cheng
176
H-Y, Corbett MS, Eldridge SM, Hernán MA, Hopewell S, Hróbjartsson A, Junqueira DR, Jüni
177
P, Kirkham JJ, Lasserson T, Li T, McAleenan A, Reeves BC, Shepperd S, Shrier I, Stewart
178
LA, Tilling K, White IR, Whiting PF, Higgins JPT. RoB 2: a revised tool for assessing risk of
179
bias in randomised trials. BMJ 2019; 366: l4898.
180
181
8) Gheibi, N., Shakhsi Niaee, M., Namdar, P., Allami, A., Zolghadr, L., & Javadi, A. et al.
182
(2021). Ivermectin as an adjunct treatment for hospitalized adult COVID-19 patients: A
183
randomized multi-center clinical trial. Asian Pacific Journal Of Tropical Medicine, 14(6), 266.
184
doi: 10.4103/1995-7645.318304
185
186
9) Okumuş, N., Demirtürk, N., Çetinkaya, R., Güner, R., Avcı, İ., & Orhan, S. et al. (2021).
187
Evaluation of the effectiveness and safety of adding ivermectin to treatment in severe
188
COVID-19 patients. BMC Infectious Diseases, 21(1). doi: 10.1186/s12879-021-06104-9
189
Downloaded from https://academic.oup.com/ofid/advance-article/doi/10.1093/ofid/ofab645/6509922 by guest on 18 January 2022
Accepted Manuscript
190
10) Hashim, H., Maulood, M., Rasheed, A., Fatak, D., Kabah, K., & Abdulamir, A. (2020).
191
Controlled randomized clinical trial on using Ivermectin with Doxycycline for treating COVID-
192
19 patients in Baghdad, Iraq. doi: 10.1101/2020.10.26.20219345
193
194
11) Elgazzar Aea. Efficacy and Safety of Ivermectin for Treatment and prophylaxis of
195
COVID-19 Pandemic [retracted]. Research Square. 2021.
196
197
12) Reardon S. Flawed ivermectin preprint highlights challenges of COVID drug studies.
198
Nature. 2021; 596, 173-174
199
200
13) Samaha AA, Mouawia H, Fawaz M, Hassan H, Salami A, Bazzal AA, et al. Effects of a
201
Single Dose of Ivermectin on Viral and Clinical Outcomes in Asymptomatic SARS-CoV-2
202
Infected Subjects: A Pilot Clinical Trial in Lebanon. Viruses. 2021;13(6).
203
204
14) Nitazoxanide Therapy for Patients With COVID-19 Pneumonia - Full Text View -
205
ClinicalTrials.gov. (2021). Retrieved 13 October 2021, from
206
https://clinicaltrials.gov/ct2/show/NCT04561219?cond=nitazoxanide&draw=2&rank=6
207
208
15) Gilead. Gilead Presents Additional Data on Investigational Antiviral Remdesivir for the
209
Treatment of COVID-19 2020. Retrieved 13 October 2021. Available from:
210
https://www.gilead.com/news-and-press/press-room/press-releases/2020/7/gilead-presents-
211
additional-data-on-investigational-antiviral-remdesivir-for-the-treatment-of-covid-19.
212
213
16) WHO. Repurposed Antiviral Drugs for Covid-19 — Interim WHO Solidarity Trial Results.
214
New England Journal of Medicine. 2020;384(6):497-511.
215
216
217
218
219
220
221
222
223
224
225
226
227
228
229
Downloaded from https://academic.oup.com/ofid/advance-article/doi/10.1093/ofid/ofab645/6509922 by guest on 18 January 2022
Accepted Manuscript
230
Study
Risk of bias level
Sample size
Control arm
Lopez-Medina et al
Low risk
398
1/198
Fonseca et al
Low risk
168
25/115
Zoni et al
Low risk
501
3/251
Kirti et al
Low risk
112
4/57
Rezai et al
Some concerns
69
0/34
Abd-Elsalam et al
Some concerns
164
4/82
Gonzalez et al
Some concerns
73
6/37
Mahmud et al
Some concerns
363
3/180
Niaee et al
High risk
180
11/60
Hashim et al
High risk
140
6/70
Okumus et al
High risk
60
9/30
Elgazzar et al
Apparent fraud
400
24/200
Total
2628
96/1314
Table 1: Studies included in the survival analysis4
231
Downloaded from https://academic.oup.com/ofid/advance-article/doi/10.1093/ofid/ofab645/6509922 by guest on 18 January 2022
Accepted Manuscript
Figure 1: Survival effects of ivermectin?
Downloaded from https://academic.oup.com/ofid/advance-article/doi/10.1093/ofid/ofab645/6509922 by guest on 18 January 2022
... 4 Once these RCTs were excluded, the conclusion of a clear benefit of ivermectin was no longer supported. 5 The threat posed by RCTs of questionable veracity is not confined to a particular field of medicine or health. For example, studies of this nature have been identified in systematic reviews of vitamin K for prevention of fractures, 6 7 tranexamic acid for prevention of postpartum haemorrhage 8 and psychological therapies for management of chronic pain. ...
... The INSPECT-SR tool will be developed using expert consensus in combination with empirical evidence, over five stages (figure 1): (1) a survey of experts to assemble a comprehensive list of checks for detecting problematic RCTs, (2) an evaluation of the feasibility and impact of applying the checks to RCTs in systematic reviews, (3) a Delphi survey to determine which of the checks are supported by expert consensus, culminating in (4) a consensus meeting to select checks to be included in a draft tool and to determine its format and finally (5) prospective testing of the draft tool in the production of new health systematic reviews, to allow refinement based on user feedback. ...
Protocol for the development of a tool (INSPECT-SR) to identify problematic randomised controlled trials in systematic reviews of health interventions
Article
Full-text available
  • Mar 2024
Introduction Randomised controlled trials (RCTs) inform healthcare decisions. It is now apparent that some published RCTs contain false data and some appear to have been entirely fabricated. Systematic reviews are performed to identify and synthesise all RCTs that have been conducted on a given topic. While it is usual to assess methodological features of the RCTs in the process of undertaking a systematic review, it is not usual to consider whether the RCTs contain false data. Studies containing false data therefore go unnoticed and contribute to systematic review conclusions. The INveStigating ProblEmatic Clinical Trials in Systematic Reviews (INSPECT-SR) project will develop a tool to assess the trustworthiness of RCTs in systematic reviews of healthcare-related interventions. Methods and analysis The INSPECT-SR tool will be developed using expert consensus in combination with empirical evidence, over five stages: (1) a survey of experts to assemble a comprehensive list of checks for detecting problematic RCTs, (2) an evaluation of the feasibility and impact of applying the checks to systematic reviews, (3) a Delphi survey to determine which of the checks are supported by expert consensus, culminating in, (4) a consensus meeting to select checks to be included in a draft tool and to determine its format and (5) prospective testing of the draft tool in the production of new health systematic reviews, to allow refinement based on user feedback. We anticipate that the INSPECT-SR tool will help researchers to identify problematic studies and will help patients by protecting them from the influence of false data on their healthcare. Ethics and dissemination The University of Manchester ethics decision tool was used, and this returned the result that ethical approval was not required for this project (30 September 2022), which incorporates secondary research and surveys of professionals about subjects relating to their expertise. Informed consent will be obtained from all survey participants. All results will be published as open-access articles. The final tool will be made freely available.
View
... The conflicting reports about the efficacy and safety of chloroquine, hydroxychloroquine and ivermectin are still fresh in our memory. [48][49][50] Several vaccines have been approved and deployed within the last 18 months following clinical trials in many countries. As of March 20, 2022, 6434 clinical trials on COVID-19 are listed on the WHO database. ...
COVID-19 Pandemic- Ethical Challenges for Healthcare Workers Practicing in Resource-Limited Settings
Article
Full-text available
  • Sep 2022
In this review, the ethical issues peculiar to the COVID-19 pandemics and the role of healthcare workers, especially those in resource-limited settings are x-rayed. We contend that there is a pressing ethical issue that needs urgent clarification on the rights and responsibilities of healthcare workers, especially in the current context of COVID-19 pandemic preparedness and responsiveness. We searched MEDLINE, Web of Science, EMBASE, Google Scholar, PUBMED related articles, newspaper articles, and online news sources for relevant information. The various professional codes of conduct (World Medical Association, Medical and Dental Council of Nigeria) were also consulted. The ethical principles of equitable distribution of healthcare resources, confidentiality with associated stigmatization, issues relating to duty to care by the healthcare workers and those pertaining to conduct of clinical trials and access to approved therapies or vaccines were highlighted in this study. We agree with the submission that healthcare workers only have a moral duty to treat patients with COVID-19 if the necessary protective equipment and adequate compensation are not provided. We argue that the duty of physicians and other healthcare workers to care for patients during pandemics such as COVID-19 is obligatory in the absence of required protective equipment and other forms of compensation. There is a need for the government and other stakeholders to put in place a National Pandemic /Epidemic Ethical Framework to address these identified ethical challenges.
View
... Antiviral agents developed for other diseases (e.g., HIV, viral hepatitis, and for veterinary viruses) have also been considered as potential agents to use against SARS-CoV-2, but none have been useful when rigorously evaluated in cell culture or in clinical trials [36][37][38][39][40][41]. Other medications approved for unrelated conditions (e.g., antimalarial drugs [42]; COX inhibitors [43,44]; glucocorticoids [45]; non-steroidal anti-inflammatory agents [46][47][48]; immunosuppressive monoclonal antibodies [49]; histamine blockers (H1 or H2 receptors) [50,51]; leukotriene inhibitors [52]; antioxidants [53,54]; mucolytics [55,56]; antibacterial antibiotics [57,58]; anti-fungal compounds [59]; anti-parasitic agents [60,61]; lipid lowering drugs [62]; oncology drugs [63,64]; selective serotonin uptake inhibitor antidepressants [65]; drugs used to treat diabetes [66]; lipid lowering agents [67]; dietary supplements [68,69]; and food additives [70]) have all been considered. However, most of these repurposed drugs have shown marginal or no benefit in clinical studies (discussed below). ...
Why Certain Repurposed Drugs Are Unlikely to Be Effective Antivirals to Treat SARS-CoV-2 Infections
Article
Full-text available
  • Apr 2024
Most repurposed drugs have proved ineffective for treating COVID-19. We evaluated median effective and toxic concentrations (EC50, CC50) of 49 drugs, mostly from previous clinical trials, in Vero cells. Ratios of reported unbound peak plasma concentrations, (Cmax)/EC50, were used to predict the potential in vivo efficacy. The 20 drugs with the highest ratios were retested in human Calu-3 and Caco-2 cells, and their CC50 was determined in an expanded panel of cell lines. Many of the 20 drugs with the highest ratios were inactive in human Calu-3 and Caco-2 cells. Antivirals effective in controlled clinical trials had unbound Cmax/EC50 ≥ 6.8 in Calu-3 or Caco-2 cells. EC50 of nucleoside analogs were cell dependent. This approach and earlier availability of more relevant cultures could have reduced the number of unwarranted clinical trials.
View
... 93,94 Politicians and other public figures have also played a significant role in shaping public perceptions and responses to the pandemic and science more broadly; promoting unproven treatments or remedies for COVID-19, such as hydroxychloroquine or ivermectin, despite a lack of scientific evidence supporting their use. 95,96 This has also led to an alarming decline in vaccine uptake that could result in outbreaks of diseases such as measles, with such outbreaks thought to be almost unheard-of pre-pandemic. [97][98][99] Others have downplayed the importance of public health measures like social distancing and wearing masks, 100,101 despite overwhelming evidence that these measures can help slow the spread of COVID-19 and other respiratory viruses. ...
“Spine to the future”—A narrative review of anatomy engagement
Article
Full-text available
  • Apr 2024
Anatomy has been integral to medical and health education for centuries, it has also had a significant role in wider public life, as an educational resource, a link to their health, and also as a darker deterrent. Historically, public engagement in anatomy is hallmarked by public dissections of convicted criminals across the globe. Artists, specifically non‐medical men, such as Leonardo da Vinci, are reported to have participated in public dissection. Dissection would later rekindle public interest in anatomy as graverobbing led to the reform and regulation of anatomy in many countries. In recent years, there has been growing interest from the public in learning more about their bodies as health and well‐being become of paramount importance, particularly following the COVID‐19 pandemic. Anatomy sits in a prime position to direct and instigate conversations around health, well‐being, and body image. Every human on earth possesses a perfect resource to look at and learn about. Models, art‐based anatomical activities, and crafts provide active learning opportunities for the wider public around anatomy. Most recently, apps, games, and extended reality provide novel and insightful learning opportunities for the public relating to the body. Finally, training and resources must also be made available from institutions and professional bodies to anatomists to enable them to deliver engagement in an already congested and educationally heavy schedule. This resurgence of interest in anatomical public engagement sees anatomy re‐enter the public spotlight, with more appropriate resources and educational settings to offer engagement with the aim of benefiting the public.
View
... These retractions affected the results of a meta-analysis that initially supported the use of the medicine. After excluding data from retracted and questionable studies, the effect did not reach statistical significance (3). In actuality, the administration of the drug aiming to prevent or treat COVID-19 has caused severe adverse events in some people (4,5). ...
Characteristics of retracted research papers before and during the COVID-19 pandemic
Article
Full-text available
  • Jan 2024
Objectives During the COVID-19 pandemic, a large number of research papers were published, and some of them were retracted. The present study aims to reveal the characteristics of retracted papers before and during the pandemic. Methods The study investigated 24,542,394 publications from 1999 to 2022 and analyzed the profiles of retracted papers from the perspectives of year, disease category, country, and journal. Results Retraction rates were generally increasing at least until 2019, and were the highest for “Neoplasms.” The number of publications for “Infections” and “Respiratory Tract Diseases” dramatically rose during the COVID-19 pandemic; however, the retraction rates in the two categories or of COVID-19-related papers were not especially high compared to other diseases. The association with retraction was strongest for China in most disease categories, whereas for COVID-19 papers, other countries showed higher retraction rates than China. In recent years, retracted papers have become less likely to be published in high-impact journals. Conclusion The COVID-19 pandemic does not seem to affect the retractions of research papers much. We should keep monitoring retractions and analyze the effects of pandemics for better science.
View
... Ivermektien se gebruik teen COVID-19 val op die grens tussen wetenskap en pseudowetenskap. Heelwat van die navorsing wat ivermektien se potensiaal uitlig, is gegrond op onetiese en oneerlike navorsingspraktyke (Lawrence et al., 2021;Hill et al., 2022a;Hill et al., 2022b;Izcovich et al., 2022;Meyerowitz-Katz et al., 2022;Taccone, Hites & Dauby, 2022). Ander studies het daarop gedui dat ivermektien nie die mortaliteitsrisiko of die risiko van meganiese ventilasievereiste verminder nie (Roman et al., 2021;Izcovich et al., 2022;Marcolino et al., 2022;Bibbins-Domingo & Malani, 2023;Naggie et al., 2023). ...
Samesweringsteorieë en vals nuus in leserskommentaar op nuusberigte van Maroela Media tydens die COVID-19-pandemie
Article
Full-text available
  • Dec 2023
Sedert die uitbreking van die COVID-19-pandemie laat in 2019, het dit die wêreld op ongekende maniere ontwrig. Die virus het tot miljoene sterftes gelei, wat veroorsaak het dat regerings inperkings en reisbeperkings ingestel het, wat ekonomieë ernstig beïnvloed het. Suid-Afrika was geen uitsondering nie, en die Suid-Afrikaanse regering het streng maatreëls ingestel om die verspreiding van die virus te bekamp, insluitende die sluiting van skole en besighede. Die pandemie het gepaardgegaan met 'n vlaag vals inligting en samesweringsteorieë, aangevuur deur sosiale media en ander aanlyn platforms. Vals inligting het die aanbeveling van onbewese geneesmiddels en behandelings vir COVID-19 ingesluit, terwyl sameswerings-teorieë gewissel het van bewerings dat die virus 'n klug is, tot bespiegelings dat dit doelbewus in 'n wapenlaboratorium geskep is. Hierdie vals inligting en samesweringsteorieë het gelei tot verwarring en wantroue in owerhede, wat pogings ondermyn het om die verspreiding van die virus te beheer.
View
... However, trials with an ivermectin treatment arm showed persistently more rapid reporting. This is notable given the serious concerns raised around both fraud and overall trial quality within ivermectin COVID-19 research [38,39]. Also notable is the relatively low reporting rate of stem cell trials. ...
Dissemination of Registered COVID-19 Clinical Trials (DIRECCT): a cross-sectional study
Article
Full-text available
  • Nov 2023
  • BMC MED
Background The results of clinical trials should be completely and rapidly reported during public health emergencies such as COVID-19. This study aimed to examine when, and where, the results of COVID-19 clinical trials were disseminated throughout the first 18 months of the pandemic. Methods Clinical trials for COVID-19 treatment or prevention were identified from the WHO ICTRP database. All interventional trials with a registered completion date ≤ 30 June 2021 were included. Trial results, published as preprints, journal articles, or registry results, were located using automated and manual techniques across PubMed, Google Scholar, Google, EuropePMC, CORD-19, the Cochrane COVID-19 Study Register, and clinical trial registries. Our main analysis reports the rate of dissemination overall and per route, and the time from registered completion to results using Kaplan–Meier methods, with additional subgroup and sensitivity analyses reported. Results Overall, 1643 trials with completion dates ranging from 46 to 561 days prior to the start of results searches were included. The cumulative probability of reporting was 12.5% at 3 months from completion, 21.6% at 6 months, and 32.8% at 12 months. Trial results were most commonly disseminated in journals (n = 278 trials, 69.2%); preprints were available for 194 trials (48.3%), 86 (44.3%) of which converted to a full journal article. Trials completed earlier in the pandemic were reported more rapidly than those later in the pandemic, and those involving ivermectin were more rapidly reported than other common interventions. Results were robust to various sensitivity analyses except when considering only trials in a “completed” status on the registry, which substantially increased reporting rates. Poor trial registry data on completion status and dates limits the precision of estimates. Conclusions COVID-19 trials saw marginal increases in reporting rates compared to standard practice; most registered trials failed to meet even the 12-month non-pandemic standard. Preprints were common, complementing journal publication; however, registries were underutilized for rapid reporting. Maintaining registry data enables accurate representation of clinical research; failing to do so undermines these registries’ use for public accountability and analysis. Addressing rapid reporting and registry data quality must be emphasized at global, national, and institutional levels.
View
... For example, the spreadsheet purportedly containing the data from one of these trials featured repeating blocks of data (4). Once these RCTs were excluded, the conclusion of a clear benefit of ivermectin was no longer supported (5). The threat posed by RCTs of questionable veracity is not confined to a particular field of medicine or health. ...
Protocol for the development of a tool (INSPECT-SR) to identify problematic randomised controlled trials in systematic reviews of health interventions
Preprint
Full-text available
  • Sep 2023
Introduction Randomised controlled trials (RCTs) inform healthcare decisions. It is now apparent that some published RCTs contain false data, and some appear to have been entirely fabricated. Systematic reviews are performed to identify and synthesise all RCTs that have been conducted on a given topic. While it is usual to assess methodological features of the RCTs in the process of undertaking a systematic review, it is not usual to consider whether the RCTs contain false data. Studies containing false data therefore go unnoticed, and contribute to systematic review conclusions. The INSPECT-SR project will develop a tool to assess the trustworthiness of RCTs in systematic reviews of healthcare related interventions. Methods and analysis The INSPECT-SR tool will be developed using expert consensus in combination with empirical evidence, over five stages: 1) a survey of experts to assemble a comprehensive list of checks for detecting problematic RCTs, 2) an evaluation of the feasibility and impact of applying the checks to systematic reviews, 3) a Delphi survey to determine which of the checks are supported by expert consensus, culminating in 4) a consensus meeting to select checks to be included in a draft tool and to determine its format, 5) prospective testing of the draft tool in the production of new health systematic reviews, to allow refinement based on user feedback. We anticipate that the INSPECT-SR tool will help researchers to identify problematic studies, and will help patients by protecting them from the influence of false data on their healthcare.
View
Prescribing Patterns of Nonrecommended Medications for Children With Acute COVID-19
Article
  • May 2024
  • Pediatrics
OBJECTIVE Repurposed medications for acute coronavirus disease 2019 (COVID-19) continued to be prescribed after results from rigorous studies and national guidelines discouraged use. We aimed to describe prescribing rates of nonrecommended medications for acute COVID-19 in children, associations with demographic factors, and provider type and specialty. METHODS In this retrospective cohort of children <18 years in a large United States all-payer claims database, we identified prescriptions within 2 weeks of an acute COVID-19 diagnosis. We calculated prescription rate, performed multivariable logistic regression to identify risk factors, and described prescriber type and specialty during nonrecommended periods defined by national guidelines. RESULTS We identified 3 082 626 COVID-19 diagnoses in 2 949 118 children between March 7, 2020 and December 31, 2022. Hydroxychloroquine (HCQ) and ivermectin were prescribed in 0.03% and 0.14% of COVID-19 cases, respectively, during nonrecommended periods (after September 12, 2020 for HCQ and February 5, 2021 for ivermectin) with considerable variation by state. Prescription rates were 4 times the national average in Arkansas (HCQ) and Oklahoma (ivermectin). Older age, nonpublic insurance, and emergency department or urgent care visit were associated with increased risk of either prescription. Additionally, residence in nonurban and low-income areas was associated with ivermectin prescription. General practitioners had the highest rates of prescribing. CONCLUSIONS Although nonrecommended medication prescription rates were low, the overall COVID-19 burden translated into high numbers of ineffective and potentially harmful prescriptions. Understanding overuse patterns can help mitigate downstream consequences of misinformation. Reaching providers and parents with clear evidence-based recommendations is crucial to children’s health.
View
The selective effect of Ivermectin on different human coronaviruses; in-vitro study
Preprint
Full-text available
  • Apr 2024
Background: The outbreak of coronavirus disease COVID-19, caused by Severe Acute Respiratory Coronavirus-2 (SARS-CoV-2) has become an urgent public health concern worldwide. Although several clinical trials have pointed to new drugs with some anti-COVID-19 activity, we are far from having a safe and effective drug. In this study, we tested the effect of ivermectin on several coronaviruses (serotypes), including variants of SARS-CoV-2. Methods: The effect of ivermectin was tested on cells infected with four different coronaviruses: NL63 (Alphacoronavirus genus.), OC43, SARS-CoV-2, and Omicron (all Betacoronavirus genus). Two hours post-infection, different doses of ivermectin were added to the cell culture. Results: There was no effect of even a high dose of ivermectin on NL63, however, we found a significant effect on OC43 PFU with a 40% inhibition at a dose of 5M. The impact of ivermectin on SARS-CoV-2 and on its Omicron variant was much more pronounced and at a dose of 5M there was inhibition of 90% and 95% respectively. Discussion: Although coronaviruses have been recognized as human pathogens for more than 50 years, no effective treatment strategy exists. Our current study did not demonstrate any effect of ivermectin on Alphacoronavirus but it had a specific impact on the Betacoronavirus genus with a mild impact on OC43 and a decidedly pronounced effect on SARS-CoV-2 including its Omicron variant. Ivermectin should be further studied as a single agent or as part of combined treatment against Coronaviruses.
View
View
Meta-analysis of Randomized Trials of Ivermectin to Treat SARS-CoV-2 Infection
Article
Full-text available
  • Jul 2021
Ivermectin is an antiparasitic drug being investigated for repurposing against SARS-CoV-2. Ivermectin showed in-vitro activity against SARS-COV-2 at high concentrations. This meta-analysis investigated ivermectin in 24 randomized clinical trials (3328 patients) identified through systematic searches of PUBMED, EMBASE, MedRxiv and trial registries. Ivermectin was associated with reduced inflammatory markers (C-Reactive Protein, d-dimer and ferritin) and faster viral clearance by PCR. Viral clearance was treatment dose- and duration-dependent. In 11 randomized trials of moderate/severe infection, there was a 56% reduction in mortality (Relative Risk 0.44 [95%CI 0.25-0.77]; p=0.004; 35/1064 (3%) deaths on ivermectin; 93/1063 (9%) deaths in controls) with favorable clinical recovery and reduced hospitalization. Many studies included were not peer reviewed and a wide range of doses were evaluated. Currently, WHO recommends the use of ivermectin only inside clinical trials. A network of large clinical trials is in progress to validate the results seen to date.
View
Ivermectin as an adjunct treatment for hospitalized adult COVID-19 patients: A randomized multi-center clinical trial
Article
Full-text available
  • Jun 2021
Objective: To evaluate different doses of ivermectin in adult patients with mild COVID-19 and to evaluate the effect of ivermectin on mortality and clinical consequences. Methods: A randomized, double-blind, placebo-controlled, multicenter clinical trial was performed at five hospitals. A total of 180 mild hospitalized patients with COVID-19 confirmed by PCR or chest image tests were enrolled and allocated to six arms including hydroxychloroquine 200 mg twice per day, placebo plus hydroxychloroquine 200 mg twice per day, single dose ivermectin (200 μg/kg), three low interval doses of ivermectin (200, 200, 200 μg/kg), single dose ivermectin (400 μg/kg), and three high interval doses of ivermectin (400, 200, 200 μg/kg). The primary endpoint of this trial was all-cause of mortality or clinical recovery. The radiographic findings, hospitalization and low O2 saturation duration, and hematological variables of blood samples were analyzed. Results: A total of 16.7% (5/30) and 20.0% (6/30) patients died in arms treated with hydroxychloroquine 200 mg twice per day and placebo plus hydroxychloroquine 200 mg twice per day, respectively, and a reduction in mortality rate in patients receiving ivermectin treatment to 0%, 10%, 0% and 3.3% for arms 1-4 were observed. Risk of mortality was also decreased about 15% in the ivermectin treated arms. Conclusions: Ivermectin as an adjunct reduces the rate of mortality, time of low O2 saturation, and duration of hospitalization in adult COVID-19 patients. The improvement of other clinical parameters shows that ivermectin, with a wide margin of safety, had a high therapeutic effect on COVID-19.
View
Ivermectin for Prevention and Treatment of COVID-19 Infection: A Systematic Review, Meta-analysis, and Trial Sequential Analysis to Inform Clinical Guidelines
Article
Full-text available
  • Jun 2021
  • Am J Therapeut
Background: Repurposed medicines may have a role against the SARS-CoV-2 virus. The antiparasitic ivermectin, with antiviral and anti-inflammatory properties, has now been tested in numerous clinical trials. Areas of uncertainty: We assessed the efficacy of ivermectin treatment in reducing mortality, in secondary outcomes, and in chemoprophylaxis, among people with, or at high risk of, COVID-19 infection. Data sources: We searched bibliographic databases up to April 25, 2021. Two review authors sifted for studies, extracted data, and assessed risk of bias. Meta-analyses were conducted and certainty of the evidence was assessed using the GRADE approach and additionally in trial sequential analyses for mortality. Twenty-four randomized controlled trials involving 3406 participants met review inclusion. Therapeutic advances: Meta-analysis of 15 trials found that ivermectin reduced risk of death compared with no ivermectin (average risk ratio 0.38, 95% confidence interval 0.19-0.73; n = 2438; I2 = 49%; moderate-certainty evidence). This result was confirmed in a trial sequential analysis using the same DerSimonian-Laird method that underpinned the unadjusted analysis. This was also robust against a trial sequential analysis using the Biggerstaff-Tweedie method. Low-certainty evidence found that ivermectin prophylaxis reduced COVID-19 infection by an average 86% (95% confidence interval 79%-91%). Secondary outcomes provided less certain evidence. Low-certainty evidence suggested that there may be no benefit with ivermectin for "need for mechanical ventilation," whereas effect estimates for "improvement" and "deterioration" clearly favored ivermectin use. Severe adverse events were rare among treatment trials and evidence of no difference was assessed as low certainty. Evidence on other secondary outcomes was very low certainty. Conclusions: Moderate-certainty evidence finds that large reductions in COVID-19 deaths are possible using ivermectin. Using ivermectin early in the clinical course may reduce numbers progressing to severe disease. The apparent safety and low cost suggest that ivermectin is likely to have a significant impact on the SARS-CoV-2 pandemic globally.
View
Review of the Emerging Evidence Demonstrating the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19
Article
Full-text available
  • Apr 2021
  • Am J Therapeut
Background: After COVID-19 emerged on U.S shores, providers began reviewing the emerging basic science, translational, and clinical data to identify potentially effective treatment options. In addition, a multitude of both novel and repurposed therapeutic agents were used empirically and studied within clinical trials. Areas of uncertainty: The majority of trialed agents have failed to provide reproducible, definitive proof of efficacy in reducing the mortality of COVID-19 with the exception of corticosteroids in moderate to severe disease. Recently, evidence has emerged that the oral antiparasitic agent ivermectin exhibits numerous antiviral and anti-inflammatory mechanisms with trial results reporting significant outcome benefits. Given some have not passed peer review, several expert groups including Unitaid/World Health Organization have undertaken a systematic global effort to contact all active trial investigators to rapidly gather the data needed to grade and perform meta-analyses. Data sources: Data were sourced from published peer-reviewed studies, manuscripts posted to preprint servers, expert meta-analyses, and numerous epidemiological analyses of regions with ivermectin distribution campaigns. Therapeutic advances: A large majority of randomized and observational controlled trials of ivermectin are reporting repeated, large magnitude improvements in clinical outcomes. Numerous prophylaxis trials demonstrate that regular ivermectin use leads to large reductions in transmission. Multiple, large "natural experiments" occurred in regions that initiated "ivermectin distribution" campaigns followed by tight, reproducible, temporally associated decreases in case counts and case fatality rates compared with nearby regions without such campaigns. Conclusions: Meta-analyses based on 18 randomized controlled treatment trials of ivermectin in COVID-19 have found large, statistically significant reductions in mortality, time to clinical recovery, and time to viral clearance. Furthermore, results from numerous controlled prophylaxis trials report significantly reduced risks of contracting COVID-19 with the regular use of ivermectin. Finally, the many examples of ivermectin distribution campaigns leading to rapid population-wide decreases in morbidity and mortality indicate that an oral agent effective in all phases of COVID-19 has been identified.
View
Evaluation of the effectiveness and safety of adding ivermectin to treatment in severe COVID-19 patients
Article
Full-text available
  • May 2021
  • BMC INFECT DIS
Background and objectives An effective treatment option is not yet available for SARS-CoV2, which causes the COVID-19 pandemic and whose effects are felt more and more every day. Ivermectin is among the drugs whose effectiveness in treatment has been investigated. In this study; it was aimed to investigate the presence of gene mutations that alter ivermectin metabolism and cause toxic effects in patients with severe COVID-19 pneumonia, and to evaluate the effectiveness and safety of ivermectin use in the treatment of patients without mutation. Materials and methods Patients with severe COVID19 pneumonia were included in the study, which was planned as a prospective, randomized, controlled, single-blind phase 3 study. Two groups, the study group and the control group, took part in the study. Ivermectin 200 mcg/kg/day for 5 days in the form of a solution prepared for enteral use added to the reference treatment protocol -hydroxychloroquine + favipiravir + azithromycin- of patients included in the study group. Patients in the control group were given only reference treatment with 3 other drugs without ivermectin. The presence of mutations was investigated by performing sequence analysis in the mdr1/abcab1 gene with the Sanger method in patients included in the study group according to randomization. Patients with mutations were excluded from the study and ivermectin treatment was not continued. Patients were followed for 5 days after treatment. At the end of the treatment and follow-up period, clinical response and changes in laboratory parameters were evaluated. Results A total of 66 patients, 36 in the study group and 30 in the control group were included in the study. Mutations affecting ivermectin metabolism was detected in genetic tests of six (16.7%) patients in the study group and they were excluded from the study. At the end of the 5-day follow-up period, the rate of clinical improvement was 73.3% (22/30) in the study group and was 53.3% (16/30) in the control group ( p = 0.10 ). At the end of the study, mortality developed in 6 patients (20%) in the study group and in 9 (30%) patients in the control group ( p = 0.37 ). At the end of the follow-up period, the average peripheral capillary oxygen saturation (SpO2) values of the study and control groups were found to be 93.5 and 93.0%, respectively. Partial pressure of oxygen (PaO2)/FiO2 ratios were determined as 236.3 ± 85.7 and 220.8 ± 127.3 in the study and control groups, respectively. While the blood lymphocyte count was higher in the study group compared to the control group (1698 ± 1438 and 1256 ± 710, respectively) at the end of the follow-up period ( p = 0.24 ); reduction in serum C-reactive protein (CRP), ferritin and D-dimer levels was more pronounced in the study group ( p = 0.02, p = 0.005 and p = 0.03 , respectively). Conclusions According to the findings obtained, ivermectin can provide an increase in clinical recovery, improvement in prognostic laboratory parameters and a decrease in mortality rates even when used in patients with severe COVID-19. Consequently, ivermectin should be considered as an alternative drug that can be used in the treatment of COVID-19 disease or as an additional option to existing protocols.
View
Repurposed Antiviral Drugs for Covid-19 — Interim WHO Solidarity Trial Results
Article
Full-text available
  • Dec 2020
Background World Health Organization expert groups recommended mortality trials of four repurposed antiviral drugs — remdesivir, hydroxychloroquine, lopinavir, and interferon beta-1a — in patients hospitalized with coronavirus disease 2019 (Covid-19). Methods We randomly assigned inpatients with Covid-19 equally between one of the trial drug regimens that was locally available and open control (up to five options, four active and the local standard of care). The intention-to-treat primary analyses examined in-hospital mortality in the four pairwise comparisons of each trial drug and its control (drug available but patient assigned to the same care without that drug). Rate ratios for death were calculated with stratification according to age and status regarding mechanical ventilation at trial entry. Results At 405 hospitals in 30 countries, 11,330 adults underwent randomization; 2750 were assigned to receive remdesivir, 954 to hydroxychloroquine, 1411 to lopinavir (without interferon), 2063 to interferon (including 651 to interferon plus lopinavir), and 4088 to no trial drug. Adherence was 94 to 96% midway through treatment, with 2 to 6% crossover. In total, 1253 deaths were reported (median day of death, day 8; interquartile range, 4 to 14). The Kaplan–Meier 28-day mortality was 11.8% (39.0% if the patient was already receiving ventilation at randomization and 9.5% otherwise). Death occurred in 301 of 2743 patients receiving remdesivir and in 303 of 2708 receiving its control (rate ratio, 0.95; 95% confidence interval [CI], 0.81 to 1.11; P=0.50), in 104 of 947 patients receiving hydroxychloroquine and in 84 of 906 receiving its control (rate ratio, 1.19; 95% CI, 0.89 to 1.59; P=0.23), in 148 of 1399 patients receiving lopinavir and in 146 of 1372 receiving its control (rate ratio, 1.00; 95% CI, 0.79 to 1.25; P=0.97), and in 243 of 2050 patients receiving interferon and in 216 of 2050 receiving its control (rate ratio, 1.16; 95% CI, 0.96 to 1.39; P=0.11). No drug definitely reduced mortality, overall or in any subgroup, or reduced initiation of ventilation or hospitalization duration. Conclusions These remdesivir, hydroxychloroquine, lopinavir, and interferon regimens had little or no effect on hospitalized patients with Covid-19, as indicated by overall mortality, initiation of ventilation, and duration of hospital stay. (Funded by the World Health Organization; ISRCTN Registry number, ISRCTN83971151; ClinicalTrials.gov number, NCT04315948.)
View
Controlled randomized clinical trial on using Ivermectin with Doxycycline for treating COVID-19 patients in Baghdad, Iraq
Preprint
Full-text available
  • Oct 2020
Objectives COVID-19 patients suffer from the lack of curative therapy. Hence, there is an urgent need to try repurposed old drugs on COVID-19. Methods Randomized controlled study on 70 COVID-19 patients (48 mild-moderate, 11 severe, and 11 critical patients) treated with 200ug/kg PO of Ivermectin per day for 2-3 days along with 100mg PO doxycycline twice per day for 5-10 days plus standard therapy; the second arm is 70 COVID-19 patients (48 mild-moderate and 22 severe and zero critical patients) on standard therapy. The time to recovery, the progression of the disease, and the mortality rate were the outcome-assessing parameters. Results among all patients and among severe patients, 3/70 (4.28%) and 1/11 (9%), respectively progressed to a more advanced stage of the disease in the Ivermectin-Doxycycline group versus 7/70 (10%) and 7/22 (31.81%), respectively in the control group (P>0.05). The mortality rate was 0/48 (0%), 0/11 (0%), and 2/11 (18.2%) in mild-moderate, severe, and critical COVID-19 patients, respectively in Ivermectin-Doxycycline group versus 0/48 (0%), and 6/22 (27.27%) in mild-moderate and severe COVID-19 patients, respectively in standard therapy group (p=0.052). Moreover, the mean time to recovery was 6.34, 20.27, and 24.13 days in mild-moderate, severe, and critical COVID-19 patients, respectively in Ivermectin-Doxycycline group versus 13.66 and 24.25 days in mild-moderate and severe COVID-19 patients, respectively in standard therapy group (P<0.01). Conclusions Ivermectin with doxycycline reduced the time to recovery and the percentage of patients who progress to more advanced stage of disease; in addition, Ivermectin with doxycycline reduced mortality rate in severe patients from 22.72% to 0%; however, 18.2% of critically ill patients died with Ivermectin and doxycycline therapy. Taken together, the earlier administered Ivermectin with doxycycline, the higher rate of successful therapy.
View
The FDA-approved Drug Ivermectin inhibits the replication of SARS-CoV-2 in vitro
Article
Full-text available
  • Apr 2020
  • ANTIVIR RES
Although several clinical trials are now underway to test possible therapies, the worldwide response to the COVID-19 outbreak has been largely limited to monitoring/containment. We report here that Ivermectin, an FDA-approved anti-parasitic previously shown to have broad-spectrum anti-viral activity in vitro, is an inhibitor of the causative virus (SARS-CoV-2), with a single addition to Vero-hSLAM cells 2 hours post infection with SARS-CoV-2 able to effect ∼5000-fold reduction in viral RNA at 48 h. Ivermectin therefore warrants further investigation for possible benefits in humans.
View
Flawed ivermectin preprint highlights challenges of COVID drug studies
Article
  • Aug 2021
  • NATURE
The study’s withdrawal from a preprint platform deals a blow to the anti-parasite drug’s chances as a COVID treatment, researchers say. The study’s withdrawal from a preprint platform deals a blow to the anti-parasite drug’s chances as a COVID treatment, researchers say. Credit: Rodrigo Urzagasti/Reuters/Alamy A man holds a bottle of anti-parasite drug ivermectin after buying it in Santa Cruz, Bolivia. A man holds a bottle of anti-parasite drug ivermectin after buying it in Santa Cruz, Bolivia.
View