Authors: Patel AN, Desai SS, Grainger DW, Mehra MR
Abstract
Importance: There is no established anti-viral therapy for treating COVID-19 illness.
Objective: To study the usefulness of Ivermectin, an antimicrobial therapy, in COVID-19 outcomes.
Design: An international, multicenter, observational propensity-score matched case-controlled study using prospectively collected data on patients diagnosed with COVID-19 between January 1, 2020 and March 31, 2020.
Setting: An international multi- institutional deidentified healthcare outcomes database.
Participants: Hospitalized patients diagnosed with COVID-19 determined by presence of a positive laboratory finding confirming SARS-CoV-2 infection.
Exposure: Ivermectin (150mcg/Kg) administered once compared with COVID-19 patients receiving medical therapy without ivermectin.
Main Outcome: The principal outcome was to assess the association of ivermectin administration with survival in COVID-19.
Results: The cohort (including 704 ivermectin treated and 704 controls) was derived from 169 hospitals across 3 continents with COVID-19 illness. The patients were matched for age, sex, race or ethnicity, comorbidities and a illness severity score (qSOFA). Of those requiring mechanical ventilation fewer patients died in the ivermectin group (7.3% versus 21.3%) and overall death rates were lower with ivermectin (1.4% versus 8.5%; HR 0.20 CI 95% 0.11-0.37, p<0.0001).
Conclusions and Relevance: The administration of ivermectin during COVID-19 illness in hospitalized patients is associated with a lower mortality and hospital length of stay. These findings require confirmation in randomized controlled trials. As the pursuit to discover anti-viral therapy for treatment of COVID-19 illness continues, a new candidate has emerged. Ivermectin, an anthelmintic drug, introduced several decades ago, is noted to reduce SARS-CoV-2 viral RNA replication in a laboratory study2. Importin (IMP) α/β1 30 is a heterodimer that binds to the SARS-CoV-2 cargo protein and moves it into the nucleus which reduces the host cell antiviral response. Ivermectin destabilizes the Impα/β1 heterodimer, prevents it from viral protein binding and thus from entering the nucleus. 2,3 These in-vitro findings have not been translated clinically to the bedside. We undertook a study to evaluate the clinical usefulness of Ivermectin in hospitalized patients with COVID-19.
Methods: This was an international, multicenter, observational propensity-score matched case-controlled study using prospectively collected data on patients diagnosed with COVID-19 between January 1, 2020 and March 31, 2020. De-identified data on patients and their outcome were obtained from a registry (Surgical Outcomes Collaborative, Surgisphere Corporation, Chicago, IL). This international research collaboration is comprised of hospitals located throughout the world. The registry ensures compliance with the FDA’s guidance on Real-World Evidence. Real-world data (RWD) is collected through automated data transfers that capture 100% of the data from each
healthcare entity at regular, predetermined intervals, thus reducing the impact of selection bias. Verifiable source documentation for the RWD elements includes electronic inpatient and outpatient medical records and data acquisition is performed through the use of a standardized data dictionary. The Collaborative utilizes a standardized Health Level 7-compliant data dictionary that serves as the focal point for all data acquisition and warehousing. Once this data dictionary is harmonized with EHR data, the majority of the data acquisition is completed using automated interfaces to expedite data transfer and improve data integrity. The data analyses are deemed exempt from ethics review.[/fusion_text][fusion_text columns="" column_min_width="" column_spacing="" rule_style="" rule_size="" rule_color="" hue="" saturation="" lightness="" alpha="" content_alignment_medium="" content_alignment_small="" content_alignment="" hide_on_mobile="small-visibility,medium-visibility,large-visibility" sticky_display="normal,sticky" class="" id="" margin_top="" margin_right="" margin_bottom="" margin_left="" fusion_font_family_text_font="" fusion_font_variant_text_font="" font_size="" line_height="" letter_spacing="" text_transform="" text_color="" animation_type="" animation_direction="left" animation_color="" animation_speed="0.3" animation_delay="0" animation_offset="" logics=""]Keywords: ivermectin, COVID-19, SARS-CoV-2
