key: cord-0055652-jek4sbj0
authors: Khan, Md. Saiful Islam; Khan, Md. Sakirul Islam; Debnath, Chitto Ranjan; Nath, Progga Nanda; Mahtab, Mamun Al; Nabeka, Hiroaki; Matsuda, Seiji; Akbar, Sheikh Mohammad Fazle
title: Ivermectin Treatment May Improve the Prognosis of Patients With COVID-19
date: 2020-12-14
journal: Arch Bronconeumol
DOI: 10.1016/j.arbr.2020.08.011
sha: 28f26ab5b7508ff298f50af75e0c543e01c385b5
doc_id: 55652
cord_uid: jek4sbj0

nan

María Teresa Gómez-Hernández a, * Nuria M. Novoa a Patricia Antúnez b Marcelo F. Jiménez a a Service of Thoracic Surgery, Salamanca University Hospital, Salamanca, Spain b Service of Anatomical Pathology, Salamanca University Hospital, Salamanca, Spain

The median age of the patients was 35 (IQR 30-43) years and 60% were men. Table 1 summarizes the demographics and clinical presentations of the two groups. At the time of admission, all patients had comparatively mild/moderate disease with cough, headache, sore throat, anosmia, breathing difficulty, and pneumonia in different proportions. Some patients in both groups had underlying comorbidities like hypertension, diabetes mellitus, asthma, and hyperlipidemia. About 13% of the patients were current smokers. Also, about 58% had higher d-dimer and CRP levels, 51% had lymphopenia, and 47% had eosinopenia. However, at the time of admission, there were no significant differences in the patient profiles, presenting symptoms, comorbidities and hemato-biochemical parameters of the two treatment groups ( Table 1) .

The treatment did not produce any aberrant symptoms related to ivermectin use. None of the ivermectin-treated patients showed progressive pathology, such as pneumonia or cardiovascular complications (Table 1) . On the other hand, 9.8% patient developed pneumonia and 1.5% had ischemic stroke those were not received ivermectin. Significantly fewer ivermectin-treated patients required oxygen inhalation (9.6% vs. 45.9), developed respiratory distress (2.6% vs. 15.8%), or needed antibiotic treatment (15.7% vs. 60.2%) and intensive care management (0.9% vs. 8.3%). Interestingly, the patients receiving ivermectin became SARS-CoV-2 negative more quickly (median 4 vs. 15 days; 95% CI, 8.97-10.59; P < 0.001). The ivermectin-treated patients also had shorter hospital stays (median 9 vs. 15 days; 95% CI, 5.09-7.51; P < 0.001). Furthermore, the mortality rate was significantly lower in the ivermectin group than SC (0.9% vs. 6.8%; P < 0.05; Table 1 ). Of the ivermectin-treated patients, 61 were randomly assigned for followup assessment 10 and 20 days after discharge; none of them reported any complications.

After SARS-CoV-2 infection, the disease generally progresses within 1 week of symptom onset due to uncontrolled viral replication in the upper respiratory tract, 2,6,11,12 followed by immune anomalies, and a cytokine storm. 2, 5, 6 Thus, an effective antiviral therapy capable of blocking viral replication at the earliest time after infection may prevent disease progression. This study shows that ivermectin is safe in COVID-19 patients and efficient at rapidly clearing SARS-CoV-2 from nasal swabs (median 4 days). This was much shorter than in the COVID-19 patients receiving only SC (15 days) or receiving a combination of three antiviral drugs (7-12 days 13 ). Furthermore, in terms of developing respiratory distress leading to ICU admission and the final outcome (discharge/death), we observed a significant clinical benefit of ivermectin in COVID-19 patients. In fact, with ivermectin, we observed quick hospital discharge (median 9 days) in 114 out of 115 patients; the remaining patient arrived with advanced disease.

Ivermectin induced rapid virological clearance that we observed in this study indicating that the preclinical efficacy of the drug against SARS-CoV-2 9 may be mirrored in patients. Such rapid clearing of SARS-CoV-2 (median 4 days); this is much shorter than the median duration (20 days) of viral shedding in patients with COVID-19, 14 indicate that ivermectin could limit the viral spreading. Collectively, the present findings suggest that ivermectin induced rapid SARS-CoV-2 clearance could reduce COVID-19 disease progression and community transmission. Although ivermectin is an anti-parasitic, its anti-viral capacities are known in both animals and human. In fact, ivermectin has been previously shown to exert antiviral activity in vitro against various viruses including dengue fever virus, zika virus, west nile virus, Venezuelan equine encephalitis virus, influenza virus, and SARS-CoV-2. 8, 9 It acts at different viral protein binding sites, reducing viral replication. Although we are not sure of the mechanisms underlying the antiviral potential of ivermectin in COVID-19 patients, the blockage of the transport of viral proteins from the cytosol to the nucleus may be one mechanism. Elucidation of the mechanisms of action of ivermectin in terms of its antiviral properties and arrest of disease progression, especially the downregulation of pneumonia, remain to be elucidated.

In conclusion, in addition to rapid SARS-CoV-2 clearance, ivermectin seems to control the course of the disease in patients with COVID-19. As of early August 2020, the numbers of COVID-19 patients are increasing worldwide; the rise is especially marked in Latin American and South Asian countries. 15 Containment strategies and patient management vary by country. Appropriate rapid management of those who are asymptomaticto-mildly/moderately symptomatic (about 90% of all patients) is essential to prevent disease progression and community spread. Therefore, given the urgent need to manage the COVID-19 patients with a safe, cheap and widely available drug, the present findings suggest that ivermectin can be considered as a first-line treatment for containing SARS-CoV-2 to prevent severe irreversible respiratory complications and community transmission. A multicenter, double-blind, drug-controlled study will strengthen our findings.

Hospital approval and patient consents were taken.

Pathophysiology, transmission diagnosis, and treatment of coronavirus disease

Virological assessment of hospitalized patients with COVID-2019

Comorbidities and mortality in patients with COVID-19 aged 60 years and older in a university hospital in Spain

The role of peripheral blood eosinophil counts in COVID-19 patients

Immune response to SARS-CoV-2 and mechanisms of immunopathological changes in COVID-19

Clinical characteristics and factors associated with long-term viral excretion in patients with SARS-CoV-2 infection: a single center 28-day study

Early antiviral treatment contributes to alleviate the severity and improve the prognosis of patients with novel coronavirus disease (COVID-19)

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The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro

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