medRxiv preprint doi: https://doi.org/10.1101/2020.06.06.20124461.this version posted June 10, 2020. The copyright holder for this preprint(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
It is made available under a CC-BY-NC-ND 4.0 International license .

ICON (Ivermectin in COvid Nineteen) study: Use of Ivermectin is Associated with Lower
Mortality in Hospitalized Patients with COVID19

Juliana Cepelowicz Rajter, M.D.

1

2

Michael S. Sherman, M.D.
Naaz Fatteh, M.D.

1

1

Fabio Vogel, Pharm. D. , BCPS
Jamie Sacks, Pharm. D.

1

1,3

Jean-Jacques Rajter, M.D.

1. Broward Health Medical Center, Fort Lauderdale, FL
2. Emeritus Professor, Drexel University College of Medicine
3. Assistant Professor, Florida International University

Corresponding author: Jean-Jacques Rajter, MD
covid19@pscflorida.com

Manuscript Word count: 2081

medRxiv preprint doi: https://doi.org/10.1101/2020.06.06.20124461.this version posted June 10, 2020. The copyright holder for this preprint(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
It is made available under a CC-BY-NC-ND 4.0 International license .

Abstract

Importance:

No therapy to date has been shown to improve survival for patients infected with SARS-

CoV-2. Ivermectin has been shown to inhibit the replication of SARS-CoV-2 in vitro but

clinical response has not been previously evaluated.

Objective:

To determine whether Ivermectin is associated with lower mortality rate in patients

hospitalized with COVID-19.

Design and Setting:

Retrospective cohort study of consecutive patients hospitalized at four Broward Healthhospitals in South Florida with confirmed SARS-CoV-2. Enrollment dates were March 15,2020 through May 11, 2020. Follow up data for all outcomes was May 19, 2020.

Participants:

280 patients with confirmed SARS-CoV-2 infection (mean age 59.6 years [standard

deviation 17.9], 45.4% female), of whom 173 were treated with ivermectin and 107

were usual care were reviewed. 27 identified patients were not reviewed due tomultiple admissions, lack of confirmed COVID results during hospitalization, age lessthan 18, pregnancy, or incarceration.

Exposure:

Patients were categorized into two treatment groups based on whether they received atleast one dose of ivermectin at any time during the hospitalization. Treatment decisions

were at the discretion of the treating physicians. Severe pulmonary involvement at

medRxiv preprint doi: https://doi.org/10.1101/2020.06.06.20124461.this version posted June 10, 2020. The copyright holder for this preprint(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
It is made available under a CC-BY-NC-ND 4.0 International license .

study entry was characterized as need for either FiO2 ≥50%, or noninvasive or invasive

mechanical ventilation.

Main Outcomes and Measures:

The primary outcome was all-cause in-hospital mortality. Secondary outcomes included

subgroup mortality in patients with severe pulmonary involvement and extubation rates

for patients requiring invasive ventilation.

Results:

Univariate analysis showed lower mortality in the ivermectin group (15.0 % versus

25.2%, OR 0.52, 95% CI 0.29-0.96, P=.03). Mortality was also lower among 75 patientswith severe pulmonary disease treated with ivermectin (38.8% vs 80.7%, OR 0.15, CI

0.05-0.47, P=.001), but there was no significant difference in successful extubation rates(36.1% vs 15.4%, OR 3.11 (0.88-11.00), p=.07). After adjustment for between-groupdifferences and mortality risks, the mortality difference remained significant for theentire cohort (OR 0.27, CI 0.09-0.85, p=.03; HR 0.37, CI 0.19-0.71, p=.03).

Conclusions and Relevance:

Ivermectin was associated with lower mortality during treatment of COVID-19,

especially in patients who required higher inspired oxygen or ventilatory support. Thesefindings should be further evaluated with randomized controlled trials.

medRxiv preprint doi: https://doi.org/10.1101/2020.06.06.20124461.this version posted June 10, 2020. The copyright holder for this preprint(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
It is made available under a CC-BY-NC-ND 4.0 International license .

Introduction

As of May 24th, 2020, the CDC recorded nearly 100,000 people having died of Covid-19

with at least 1,639,099 confirmed infections having been reported in the US and its

territories. Covid-19 presents an unprecedented challenge to identify effective therapy

for prevention and treatment. Currently, there is no evidence from randomized

controlled trials of any potential therapy improving survival outcomes in patients withconfirmed disease.

In the late 1970s Ivermectin was developed as a new class of drug to treat parasitic

infections. Initially used in veterinary Medicine, it was soon found to be safe andeffective in humans. It has successfully been used to treat onchocerciasis and lymphatic

filariasis in millions of people worldwide as part of a global drug donation program.

About 3.7 billion doses of Ivermectin have been distributed in mass drug administration

campaigns globally over the past 30 years. Presently, Ivermectin is approved for use in

humans in several countries to treat onchocerciasis, lymphatic filariasis, strongyloidiasis

1

and scabies.

Ivermectin has previously been studied as a therapeutic option for viral infections within vitro data showing some activity against a broad range of viruses, including HIV,

2,3

Dengue, Influenza and Zika virus.

In a recent study, Wagstaff et al, demonstrated that

Ivermectin was a potent in-vitro inhibitor of SARS-CoV-2, showing a 99.8% reduction in

4viral RNA after 48 hours.

However, in-vivo efficacy of ivermectin in SARS-CoV-2

infection in humans has not previously been reported.

Methods:

medRxiv preprint doi: https://doi.org/10.1101/2020.06.06.20124461.this version posted June 10, 2020. The copyright holder for this preprint(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
It is made available under a CC-BY-NC-ND 4.0 International license .

Patients

Sequentially consecutive hospitalized patients at four Broward Health associatedhospitals in South Florida with laboratory-confirmed infection with SARS-CoV-2 during

their admission were reviewed in this study. The list of confirmed cases was provided by

the epidemiology department. Enrollment dates ranged from March 15, 2020 throughMay 11, 2020. Confirmatory testing was performed by nasopharyngeal swab using an

FDA Emergency Use Authorized COVID-19 molecular assay for the detection of SARS-

CoV-2 RNA. Patients younger than 18 years old, pregnant, or incarcerated were

excluded from the data collection based on IRB requirements. Patients who had at least

2 separate admissions placing them in both groups were also excluded.

Trial procedures

Records were abstracted by four of the authors and all data was subsequently reviewed

and confirmed by the lead author. Baseline data was collected at the time of ivermectin

administration for the ivermectin group; for the usual care group baseline was either at

the time of administration of hydroxychloroquine or, if not used, at the time ofadmission. Information collected included COVID-19 testing results, patient

demographics, pre-existing comorbid conditions, initial vital signs, chest imaging studies,laboratory results, and the use of hydroxychloroquine with and without azithromycin inorder to describe the cohort and to identify potential cofounders between groups.

Severity of pulmonary involvement was assessed at the time of initiation of therapy(“onset”) and categorized as severe or non-severe. Patients were considered to havesevere pulmonary involvement if they required an FiO2 of 50% or greater, high-flow

medRxiv preprint doi: https://doi.org/10.1101/2020.06.06.20124461.this version posted June 10, 2020. The copyright holder for this preprint(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
It is made available under a CC-BY-NC-ND 4.0 International license .

nasal oxygen, noninvasive ventilation, or intubation and mechanical ventilation. The

non-severe pulmonary criteria encompassed patients who required no supplemental

oxygen, or “low FIO2” (ie: Venturi mask 40% or less, or any amount of low flow nasal

cannula), independent of radiographic or laboratory findings.

Patients were categorized into two treatment groups based on whether they received

ivermectin at any time during the hospitalization. Patients in the Ivermectin group

received at least one oral dose of ivermectin at 200 micrograms/kilogram in addition tousual clinical care. The decision to prescribe ivermectin, hydroxychloroquine,azithromycin or other medications was at the discretion of the treating physicians,

however hospital guidelines were established for the use of these agents as well as for

cardiac and QT monitoring for patients receiving hydroxychloroquine. Oxygen andventilatory support were applied per the customary care.

Outcomes

The primary outcome was all-cause in-hospital mortality. Patient was considered a“survivor” if they left the hospital alive, or if their status in the hospital changed from

active care to awaiting transfer to a skilled facility. The latter outcome was necessitatedby the requirement that two consecutive negative nasopharyngeal swab specimens for

SARS-CoV-2, collected equal to or greater than 24 hours apart, were necessary for apatient to be accepted to a skilled nursing facility.

Secondary outcomes included subgroup mortality of patients with severe pulmonary

involvement, extubation rates for patients requiring mechanical ventilation, and lengthof hospital stay.

medRxiv preprint doi: https://doi.org/10.1101/2020.06.06.20124461.this version posted June 10, 2020. The copyright holder for this preprint(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
It is made available under a CC-BY-NC-ND 4.0 International license .

Statistical analysis

Univariate analysis of the primary mortality outcome, and comparisons between

treatment groups were determined by Student’s t test or Mann-Whitney U test forcontinuous variables as appropriate, and by Pearson Chi Square test for categoricalvariables. The method of Hodges-Lehman was used to estimate median differenceswith 95% confidence intervals.

To adjust for confounders and between-group differences, a multivariate analysis was

performed using stepwise binary logistic regression. Patient variables included in theanalysis were age, sex, comorbidities of diabetes, chronic lung disease, cardiovasculardisease, and hypertension, smoking status, severity of pulmonary involvement, BMI,

peripheral white blood count, absolute lymphocyte count, and use ofhydroxychloroquine and azithromycin based on bivariate associations within our data, apriori plausibility, and documented associations with mortality from previous studies.

Adjusted odds ratio with 95% confidence intervals were computed to show level ofcertainty. Hazard ratios for the primary outcome of mortality with 95% confidence

intervals were calculated by means of the Cox regression with the same covariates.

Analyses were based on nonmissing data and missing data were not imputed.

Missingness of 1% was found for peripheral white blood cell count, 5% for smoking

status, and 7% for absolute lymphocyte count. Secondary analyses were thus also

performed on the entire cohort. All tests were 2-sided and a p value <.05 wasconsidered statistically significant. All statistical analyses were conducted using IBM

SPSS v 24.0 software.

medRxiv preprint doi: https://doi.org/10.1101/2020.06.06.20124461.this version posted June 10, 2020. The copyright holder for this preprint(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
It is made available under a CC-BY-NC-ND 4.0 International license .

Oversight

The protocol was approved by the institutional review board for the Broward Healthhospital system. The authors assume responsibility for the accuracy and completenessof the data and analyses, as well as for the fidelity of the trial.

Results

Characteristics of the patients

307 patients were admitted for COVID-19 during the time period studied.

4 patientswere not reviewed due to multiple admissions, 11 had no confirmed COVID testing at

the time of the study, and 12 were excluded due to age younger than 18 years old,

pregnancy, or incarceration. The remaining cohort of 280 patients was comprised of

173 treated with ivermectin and 107 in the usual care group. Follow up data for all

outcomes were available through May 19th, 2020. No patients were lost to follow-up

for the primary outcome. At the time of analysis, all patients in the cohort had met theendpoint of death, discharge alive, or awaiting transfer to a skilled facility.

Baseline characteristics and between group comparisons are shown in Table 1.

Characteristics were similar between groups, however hypertension was more prevalent

in the Ivermectin group, whereas the use of hydroxychloroquine andhydroxychloroquine plus azithromycin were higher in the usual care group. No othersignificant between-group differences were found among baseline characteristics orcomorbidities, including age, race, cardiac comorbidities, or smoking status.

OutcomesmedRxiv preprint doi: https://doi.org/10.1101/2020.06.06.20124461.this version posted June 10, 2020. The copyright holder for this preprint(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
It is made available under a CC-BY-NC-ND 4.0 International license .

Unadjusted outcomes for both groups are shown in Table 2. Overall mortality wassignificantly lower in the ivermectin group than in the usual care group (15.0% vs 25.2%,

for ivermectin and usual care respectively, p=.03). Mortality was also lower for

ivermectin treated patients in the subgroup of patients with severe disease (38.8% vs.

80.7%, p=.001). Differences in extubation rates between groups were not significant

and there was also no difference in length of hospital stay.

Univariate analysis found that patients dying with COVID-19 infection were older, had

higher white blood cell counts and lower absolute lymphocyte counts (Table 3a) thansurvivors. Patients who died were also more likely to have been current or former

smokers and have comorbid cardiac conditions, and were more likely to have severe

pulmonary involvement and hypotension at study entry (Table 3b). In comparison to

Caucasians, Blacks and Hispanics had lower odds of mortality in this cohort.

In the multivariate analysis, adjusting for demographic factors, between-groupdifferences in mortality risks, and concomitant use of hydroxychloroquine (with orwithout azithromycin), independent predictors of in-hospital mortality included

treatment group, age, severe pulmonary disease category, and reduced lymphocyte

count (Table 4). Similarly, the Cox regression showed ivermectin was associated with asignificantly lower hazard ratio for mortality of 0.37 (CI 0.19 - 0.70, p=.003). Complete

case analysis on the entire cohort without missing data was similar (HR 0.40, 0.22- 0.74),

p=.003).

Discussion

medRxiv preprint doi: https://doi.org/10.1101/2020.06.06.20124461.this version posted June 10, 2020. The copyright holder for this preprint(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
It is made available under a CC-BY-NC-ND 4.0 International license .

In this multihospital retrospective cohort study, we observed a significant association

with ivermectin on survival for patients admitted with Covid-19. This association was

also seen in the subset of patients with severe pulmonary disease.

Similar to other studies, we noted that older age, cardiac disease, current or former

smoking, more severe pulmonary involvement at presentation, higher white blood cellcounts, and lower lymphocyte counts emerged as risk markers for in-hospital mortality.

The overall mortality, and mortality in intubated patients, in our usual care group was

similar to what was reported in previous studies. Richardson et al reported an overallmortality of 21% in their New York City cohort, with a mortality of 88% in intubatedpatients.

5

Fei Zhou et al reported a 28.2% mortality in their cohort of hospitalized

6

patients in Wuhan, China; their intubated patients had a mortality of 96.9%.

In contrast

to Mehra et al, we did not see a mortality effect for hydroxychloroquine, with orwithout the addition of azithromycin.

7This may have been due to the small number ofpatients who were not treated with these agents; our study was underpowered todetect a difference. We also hypothesize that precautionary measures in the hospitals’

protocol for hydroxychloroquine use could have prevented them from developing fatalarrhythmias. These included baseline EKG and daily QT monitoring by telemetry for any

patient receiving hydroxychloroquine or combination therapy, avoidance ofazithromycin if patient’s baseline QTc was greater than 460msec, and discontinuation ofhydroxychloroquine if there was a concerning elevation in QTc or if the patient’s

cardiologist recommended discontinuation.

medRxiv preprint doi: https://doi.org/10.1101/2020.06.06.20124461.this version posted June 10, 2020. The copyright holder for this preprint(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
It is made available under a CC-BY-NC-ND 4.0 International license .

We did not confirm an increase risk of mortality in Blacks. This was likely due todifference in age; white patients were significantly older (66.8 vs 59.1 years; meandifference 7.7 years, CI 3.0 - 12.4, p=.001).

In the Ivermectin group, thirteen patients received a second dose of Ivermectin (200mcg/kg) on day 7, since they were still hospitalized. Due to the low numbers, we did not

perform any further analysis of the redosing. We also did not observe any significant

side-effect from Ivermectin use.

We did not observe a significant difference in hospital length of stay between thegroups (median 7 days for both groups). Possible explanation could include delay indischarging patients to other facilities (skilled nursing facilities, inpatient rehabs, etc)

due to lag in obtaining required repeat COVID testing results.

Need for mechanical ventilation was not adopted as outcome of interest, as nationalguidelines and practice patterns for intubation criteria changed throughout the lengthof the study.

We did not find a lower mortality in the non-severe patients treated with ivermectin;

however, our study was not powered to assess these differences as the overall mortality

in non-severe patients was low. Similarly, the study was not powered to determine

whether extubation rates were higher in the Ivermectin group. These should be

investigated further with a larger randomized controlled trial.

Our study has several limitations. Due to the retrospective observational nature of thestudy, despite adjustment for known cofounders, we cannot exclude the possibility of

unmeasured confounding factors. Although more of the control group was enrolledmedRxiv preprint doi: https://doi.org/10.1101/2020.06.06.20124461.this version posted June 10, 2020. The copyright holder for this preprint(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
It is made available under a CC-BY-NC-ND 4.0 International license .

earlier in the study, suggesting the possibility of timing bias, this may be offset bypreferential treatment of more severe patients with ivermectin early in the study due to

low initial availability. We also did not find consistently better mortality outcomes withtime over the short duration of this study. Most of our patients studied received

hydroxychloroquine with or without azithromycin and we are unable to determine

whether these medications had an added benefit, or whether mortality would havebeen better in both groups without these agents.

We have shown that ivermectin administration was significantly associated with lower

mortality among patients with COVID-19, particularly in patients with more severe

disease. Interpretation of these findings are tempered by the limitations of theretrospective design and the possibility of confounding. Appropriate dosing for thisindication is not known; nor are the effects of ivermectin on viral load, or in patientswith milder disease. Further studies in appropriately designed randomized trials arerecommended before any conclusions can be made.

Acknowledgements

Dr. Edward Gracely, Ph.D. for his support with the statistical analysis.

Conflicts of interest- including relevant financial interests, activities, relationships/affiliations

Juliana Cepelowicz Rajter, M.D.: none
Michael S. Sherman, M.D.: none
Naaz Fatteh, M.D.: none
Fabio Vogel, Pharm. D. , BCPS.: none
Jaime Sacks, Pharm. D.: none
Jean-Jacques Rajter, M.D.: none

medRxiv preprint doi: https://doi.org/10.1101/2020.06.06.20124461.this version posted June 10, 2020. The copyright holder for this preprint(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
It is made available under a CC-BY-NC-ND 4.0 International license .

References:

1. Navarro M, Camprubí D, Requena-Méndez A, et al. Safety of high-dose ivermectin: asystematic review and meta-analysis. J Antimicrobial Chemother. 2020; 75: 827–834.

2. Boldescu V, Behnam MAM, Vasilakis N, Klein CD. Broad-spectrum agents for flaviviral

infections: dengue, Zika and beyond. Nat Rev Drug Discov. 2017; 16:565-586.

3. Wagstaff KM, Sivakumaran H, Heaton SM, Harrich D, Jans DA. Ivermectin Is a SpecificInhibitor of Importin α/β-Mediated Nuclear Import Able to Inhibit Replication of HIV-1

and Dengue Virus. Biochem J. 2012; 443:851-856.

4. Caly L, Druce JD, Catton MG, Jans DA, Wagstaff KM. The FDA-approved drug

ivermectin inhibits the replication of SARS-CoV-2 in vitro. Antiviral Research 2020

178:104787. Doi: 10.1016/j.antiviral.2020.104787 (Epub ahead of print).

5. Safiya Richardson, Jamie S. Hirsch, Mangala Narasimha, et al. Presenting

Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With

COVID-19 in the New York City Area. JAMA. Published online April 22, 2020.

doi:10.1001/jama.2020.6775.

6. Fei Zhou, Ting Yu, Ronghui Du , et al. Clinical course and risk factors for mortality ofadult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. The

Lancet, Volume 395, Issue 10229, 28 March–3 April 2020, Pages 1054-1062.

7. Mehra MR, Desai SS, Ruschitzka F, Patel AN. Hydroxychloroquine or chloroquine withor without a macrolide for treatment of COVID-19: a multinational registry analysis.

Lancet 2020: DOI 10.1016/S0140-6736(20)31180-6 (Epub ahead of print)

medRxiv preprint doi: https://doi.org/10.1101/2020.06.06.20124461.this version posted June 10, 2020. The copyright holder for this preprint(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
It is made available under a CC-BY-NC-ND 4.0 International license .

Table 1: Patient Characteristics by Treatment Group
Demographic
characteristics
Age, yearsa
Female sex
Race ethnicity
Black
White
Hispanic
Other or not
identifiedc
Smoking
Current
FormerNever
Number ofcomorbiditiesa
Diabetes
CardiacPulmonaryObesity
Renal
CancerHypertension
Neurologic
HIV
Thyroid
BMIa
Severity
SevereNon-severeHRb
MAP (mm Hg)b
MAP < 70 mm Hg
Hydroxychloroquine
Hydroxychloroquine
plus azithromycin
Peripheral whitecell count (X 109/L) b
Lymphocyte count(X 109/L) bamean (+ SD)

Total (n=280)

Ivermectin (n=173)

P value59.6 (17.9)
127 (45.4)

Usual Care(n=107)58.6 (18.5)
43 (41.2)

60.2 (17.6)
84 (48.6)

153 (54.6)
76 (27.1)
33 (11.7)
13 (4.6)

55 (51.4)
35 (32.7)
12 (11.2)
5 (4.7)98 (56.6)
41 (23.7)
21 (12.1)
13 (7.5)

.45
.17
.36

16/255 (6.3)
30/255 (11.7)
209/255 (81.9)
1.66 (1.34)

7/99 (7.1)
15/99 (15.2)
77/99 (77.8)
1.60 (1.46)

9/156 (5.7)
15/151 (9.9)
132/151 (87.4)
1.70 (1.27)

90 (32.1)
43 (15.4)
28 (10.0)
114 (40.7)
24 (8.6)
17 (6.1)
50 (17.9)
28 (10.0)
9 (3.2)23 (8.2)
30.0 (7.8)

31 (29.0)
18 (16.8)
14 (13.1)
42 (39.3)
10 (9.4)
8 (7.5)13 (12.2)
8 (7.5)1 (1)7 (6.6)29.8 (7.2)

59 (34.1)
25 (14.5)
14 (8.9)72 (41.6)
14 (8.1)
9 (5.2)37 (21.4)
20 (11.6)
8 (4.6)16 (9.3)
30.1 (8.2)

75 (26.8)
205 (73.2)
86.0 (75.0, 97.0)
93 (82.2, 103.0)
13/260 (5.0%)260 (92.9%)
241 (86.1%)

26 (24.3)
81 (75.7)
87.0 (73.5, 95.5)
91 (81.5, 104)
6/89 (6.7%)
104 (97.2)
98 (91.6)

49 (28.3)
124 (71.7)
85.5 (75.3, 98.0)
94 (83, 103)
7/171 (4.1%)
156 (90.2)
143 (82.7)

7.3 (5.6, 10.2)(n=277)
1.15 (0.78, 1.56)(n=260)7.0 (5.7, 8.9)(n=106)1.14 (.84, 1.49)(n=102)7.6 (5.5, 11.1)(n=171)1.20 (.77, 1.67)(n=158)

.40

.57
.37
.59
.18
.70
.72
.44
.05
.27
.09
.42
.81
.46
.12
.55
.65
.66
.35
.03
.04
.41
.62

medRxiv preprint doi: https://doi.org/10.1101/2020.06.06.20124461.this version posted June 10, 2020. The copyright holder for this preprint(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
It is made available under a CC-BY-NC-ND 4.0 International license .

bcmedian (interquartile range)

Asian, Native American, Pacific Islander, or not identifiedmedRxiv preprint doi: https://doi.org/10.1101/2020.06.06.20124461.this version posted June 10, 2020. The copyright holder for this preprint(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
It is made available under a CC-BY-NC-ND 4.0 International license .

Table 2: Univariate Clinical Outcomes by Treatment Group

Mortality
Total

Number/total number (%)
Total (n=280)
Control (n=107)

Ivermectin (n=173)

OR (CI)

P value

53 (18.9)27 (25.2)

26 (15.0).03

Severe40/75 (53.3)

21/26 (80.7)

19/49 (38.8)

Non-severe
Successful
extubation
Length of stay
(median, IQR)

13/205 (6.3)
17/62 (27.4)

6/81 (7.4)
4/26 (15.4)

7/124 (5.6)
13/36 (36.1)

7.0 (4.0, 12.5)

7.0 (4.0, 10.0)

7.0 (4.0, 13.3)

0.52 (0.29 to
0.96)
0.15 (0.05 to
0.47)
0.75 (0.24 to 2.3)
3.11 (0.88 to
11.00)

Abbreviations: IQR – interquartile range.

.001
.61
.07
.34

medRxiv preprint doi: https://doi.org/10.1101/2020.06.06.20124461.this version posted June 10, 2020. The copyright holder for this preprint(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
It is made available under a CC-BY-NC-ND 4.0 International license .

Table 3a: Univariate analysis of factors associated with mortality (continuous variables)

Age, yearsa
Number ofcomorbiditiesa
BMIa
Peripheral whitecell count (X 109/L)b
Lymphocyte count(X 109/L) b

Nonsurvivors

Survivors

Difference (CI)70.7 (15.1)
1.81 (1.49)

57.0 (17.6)
1.63 (1.31)

13.6 (8.5 to 18.8)
0.18 (-0.22 to 0.59)

P
value
<.001
.37

28.3 (6.7)
9.8 (6.1, 13.2)

30.3 (8.0)
7.2 (5.5, 9.25)-2.0 (-4.4 to -0.33)
2.1 (0.8 to 3.6)

.09
.001

0.77 (0.47, 1.15)

1.29 (0.90,
1.68)-0.46 (-0.63 to 0.30)

<.001

a

mean (+ SD)b

median (interquartile range)medRxiv preprint doi: https://doi.org/10.1101/2020.06.06.20124461.this version posted June 10, 2020. The copyright holder for this preprint(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
It is made available under a CC-BY-NC-ND 4.0 International license .

Table 3b: Univariate analysis of factors associated with mortality (categorical variables)

Sex
FemaleMale
Smoking
Current or former
Nonsmoker
Race
White
Black
Hispanic
OtheraComorbidities
Diabetes
CardiacPulmonaryObesity
Renal
CancerHypertension
Neurologic
Thyroid
Presentation
severity
SevereNon-severe
MAP < 70
Hydroxychloroquine
Hydroxychoroquine
plus azithromycinaMortality
Number/total(percent)

OR (CI)

P value

24/127 (18.8)
29/153 (19.0)

1.00 (0.55 to 1.83)
Reference.99

18/46 (39.1)
28/209 (13.9)

2.75 (0.14 to 0.55)
Reference<.001

22/76 (28.9)
26/153 (17.0)
3/33 (9.1)
2/18 (11.1)

Reference
0.50 (0.26 to 0.96)
0.24 (0.07 to 0.89)
0.31 (0.07 to 1.45)

.04
.02
.12

19/90 (21.1)
15/43 (34.9)
5/28 (17.9)
20/114 (17.5)
6/24 (25.0)
5/17 (29.4)
9/50 (18.0)
7/28 (25.0)
5/23 (21.7)

1.23 (0.66 to 2.30)
2.81 (1.37 to 5.75)
0.92 (0.33 to 2.55)
0.86 (0.46 to 1.59)
1.48 (0.56 to 3.94)
1.87 (0.63 to 5.55)
0.93 (0.42 to 2.05)
1.49 (0.60 to 3.72)
1.21 (0.43 to 3.42)

.52
.004
.88
.62
.43
.25
.85
.39
.72

40/75 (53.3)
13/192 (6.8)
8/13 (38.5)
50/260 (19.2)
47/241 (19.5)

16.88 (8.20 to 34.75)<.001

9.08 (2.82, 29.28)
1.35 (0.38 to 4.78)
1.33 (0.53 to 3.37)

<.001
.64
.54

Asian, Native American, Pacific Islander, or not identified.04

medRxiv preprint doi: https://doi.org/10.1101/2020.06.06.20124461.this version posted June 10, 2020. The copyright holder for this preprint(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
It is made available under a CC-BY-NC-ND 4.0 International license .

Table 4: Multivariate analysis of factors associated with mortality

Treatment group:
Ivermectin
Control
Age
Female sex
Current or former
smokerRace
Black
Hispanic
Other
Comorbidities
Diabetes
CardiacPulmonaryHypertension
BMI
Severepresentation
MAP < 70 mm Hg
Peripheral whitecell countLymphocyte countOR (CI)

P value

0.27 (0.09, 0.85)
Reference
1.05 (1.02, 1.09)
0.69 (0.25, 1.91)
3.43 (0.94, 12.48)

.03
.005
.48
.06

0.66 (0.22, 1.99)
0.14 (0.02, 1.10)
0.77 (0.06, 9.88)

.165
.464
.061
.843

1.13 (0.38, 3.36)
1.62 (0.45, 5.83)
0.15 (0.17, 1.24)
1.00 (0.22 to 4.56)
0.99 (0.90, 1.08)
26.88 (8.11, 89.05)

.83
.46
.08
.99
.77
<.001

2.10 (0.26, 7.04)
1.09 (.958, 1.24)

.73
.19

4.04 (1.35, 12.09).01