Anti-COVID property of subcutaneous ivermectin in synergy with zinc among midlife moderately symptomatic patients: a structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: The study objective is to quantify the effectiveness of ivermectin (subcutaneous/oral IVM) in the presence or absence of zinc (Zn) for clinical and radiological improvement in coronavirus disease 2019 (COVID-19) patients with moderate severity. TRIAL DESIGN: This quadruple-blinded, placebo-controlled randomized clinical trial will be a multiarmed multi-centered study with superiority framework. PARTICIPANTS: Quinquagenarian and sexagenarian patients with moderate COVID-19 symptoms and positive severe respiratory syndrome coronavirus -2 (SARS-CoV-2) PCR will be included. Participants with co-morbidities and pregnant women will be excluded. Patient recruitment will be done in Shaikh Zayed Medical Complex, Doctors Lounge and Ali Clinic in Lahore (Pakistan). INTERVENTION AND COMPARATOR: The registered patients will be allocated in 6 groups (30 participants each). Patients will be taking subcutaneous IVM at 200 µg/kg/48 h (Arm A) or subcutaneous IVM at 200 µg/kg/48 h and oral Zn 20mg/8 h (Arm B) or oral IVM at 0.2 mg/kg/day (Arm C) or oral IVM at 0.2 mg/kg/day and oral Zn 20mg/8 h (Arm D) or alone oral Zn 20mg/8 h (Arm E) or placebo alone (Arm X). Patients in all arms will receive standard care and respective placebo (empty capsule 8 hourly and/or subcutaneous normal saline 2ml/48 h). MAIN OUTCOMES: Primary endpoints will be duration of symptomatic phase and SARS-CoV-2 clearance along with high resolution CT (HRCT) chest score and clinical grade scale (CGS) on day 6. 30-day mortality will be documented as a secondary endpoint. SARS-CoV-2 clearance will be calculated by second PCR on day 7. HRCT chest score will be measured by the percentage and lung lobes involvement on day 6 with a maximum score of 25. CGS will be recorded on a seven-point scale; grade 1 (not hospitalized, no evidence of infection and resumption of normal activities), grade 2 (not hospitalized, but unable to resume normal activities), grade 3 (hospitalized, not requiring supplemental oxygen), grade 4 (hospitalized, requiring supplemental oxygen), grade 5 (hospitalized, requiring nasal high-flow oxygen therapy and/or noninvasive mechanical ventilation), grade 6 (hospitalized, requiring ECMO and/or invasive mechanical ventilation) and grade 7 (death). RANDOMISATION: A simple lottery method will be used to randomly allocate scrutinized patients in 1:1:1:1:1:1 ratio in 6 groups. BLINDING (MASKING): Patients, primary care physicians, outcome assessors and the data collection team will be blinded. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): 180 participants will be randomized into six arms with five investigational and one placebo group. TRIAL STATUS: Institutional Review Board Shaikh Zayed Post-Graduate Medical Complex, Lahore, Pakistan has approved the protocol (version 2.3) with ID SZMC/IRB/Internal0056/2020. The trial was approved on July 14, 2020, and enrolment started on July 30, 2020. The estimated completion date is October 30, 2021. TRIAL REGISTRATION: Clinical Trial has been retrospectively registered on www.clinicaltrials.gov with registration ID NCT04472585 dated July 16, 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). With the intention of expediting dissemination of this trial, the conventional formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines.

Zoonotic and reverse zoonotic events of SARS-CoV-2 and their impact on global health.

Coronaviruses (CoVs) are enveloped, positive sense, single-stranded RNA viruses. The viruses have adapted to infect a large number of animal species, ranging from bats to camels. At present, seven CoVs infect humans, of which Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is responsible for causing the Coronavirus Disease 2019 (COVID-19) in humans. Since its emergence in late 2019, SARS-CoV-2 has spread rapidly across the globe. Healthcare systems around the globe have been stretched beyond their limits posing new challenges to emergency healthcare services and critical care. The outbreak continues to jeopardize human health, social life and economy. All known human CoVs have zoonotic origins. Recent detection of SARS-CoV-2 in pet, zoo and certain farm animals has highlighted its potential for reverse zoonosis. This scenario is particularly alarming, since these animals could be potential reservoirs for secondary zoonotic infections. In this article, we highlight interspecies SARS-CoV-2 infections and focus on the reverse zoonotic potential of this virus. We also emphasize the importance of potential secondary zoonotic events and the One-Health and One-World approach to tackle such future pandemics.