#Reduction of #coronavirus #burden with mass #azithromycin distribution (Clin Infect Dis., abstract)

[Source: Clinical Infectious Diseases, full page: (LINK). Abstract, edited.]

Reduction of coronavirus burden with mass azithromycin distribution

Thuy Doan, Armin Hinterwirth, Ahmed M Arzika, Lee Worden, Cindi Chen, Lina Zhong, Catherine E Oldenburg, Jeremy D Keenan, Thomas M Lietman, MORDOR Study Group

Clinical Infectious Diseases, ciaa606, https://doi.org/10.1093/cid/ciaa606

Published: 19 May 2020

 

Abstract

We evaluated the potential antiviral effects of azithromycin on the nasopharyngeal virome of Nigerien children who had received multiple rounds of mass drug administration. We found that the respiratory burden of non-SARS coronaviruses was decreased with azithromycin distributions.

Issue Section: Brief Report

This content is only available as a PDF.

© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

Keywords: Coronavirus; Pediatrics; Azithromycin.

——

Should #Clinicians Use #Chloroquine or #Hydroxychloroquine Alone or in Combination With #Azithromycin for the #Prophylaxis or #Treatment of #COVID19?

[Source: Annals of Internal Medicine, full page: (LINK). Summary, edited.]

Should Clinicians Use Chloroquine or Hydroxychloroquine Alone or in Combination With Azithromycin for the Prophylaxis or Treatment of COVID-19?

Living Practice Points From the American College of Physicians (Version 1)

Amir Qaseem, MD, PhD, MHA, Jennifer Yost, RN, PhD, Itziar Etxeandia-Ikobaltzeta, PharmD, PhD, Matthew C. Miller, MD, George M. Abraham, MD, MPH, Adam Jacob Obley, MD, Mary Ann Forciea, MD, Janet A. Jokela, MD, MPH, Linda L. Humphrey, MD, MPH, for the Scientific Medical Policy Committee of the American College of Physicians

DOI: https://doi.org/10.7326/M20-1998

 

  • Key Question 1
    • Should Clinicians Use Chloroquine or Hydroxychloroquine Alone or in Combination With Azithromycin for Prophylaxis Against COVID-19?
  • Key Question 2
    • Should Clinicians Use Chloroquine or Hydroxychloroquine Alone or in Combination With Azithromycin for Treatment of COVID-19?

Background

Using chloroquine or hydroxychloroquine, with or without azithromycin, to prevent coronavirus disease (COVID-19) after infection with novel coronavirus (SARS-CoV-2) or to treat COVID-19 began to receive attention following preliminary reports from in vitro (1) and human (2) studies. While multiple studies are planned or under way (3, 4), it is imperative to continually synthesize the results from the best available evidence to inform point-of-care decisions about the use of chloroquine or hydroxychloroquine. These practice points are based on a rapid and living systematic evidence review conducted by the University of Connecticut Health Outcomes, Policy, and Evidence Synthesis Group and will be updated as new evidence becomes available. The practice points development and update methods are included in the Appendix. This version of the practice points, based on an evidence review conducted on 17 April 2020, was approved by the American College of Physicians Board of Regents on 4 May 2020 and submitted to Annals of Internal Medicine on 6 May 2020.

(…)

Keywords: SARS-CoV-2; COVID-19; Antivirals; Chloroquine; Azithromycin.

——

#Nitazoxanide / #azithromycin #combination for #COVID19: A suggested new protocol for early management (Pharmacol Res., abstract)

[Source: Pharmacological Research, full page: (LINK). Abstract, edited.]

Pharmacological Research | Volume 157, July 2020, 104874

Nitazoxanide/azithromycin combination for COVID-19: A suggested new protocol for early management

Mina T. Kelleni a,b

a Pharmacology Department, College of Medicine, Minia University, Egypt; b Pharmacology Department, College of Pharmacy, Jouf University, Saudi Arabia

Received 14 April 2020, Revised 23 April 2020, Accepted 24 April 2020, Available online 30 April 2020.

DOI: https://doi.org/10.1016/j.phrs.2020.104874

 

Abstract

Azithromycin has been shown to have a clinical efficacy against severe acute respiratory syndrome coronavirus 2; ivermectin has also demonstrated a remarkable experimental efficacy with a potential to be used for Coronavirus disease 2019. Further, BCG vaccination is being considered for clinical trials aiming to test its potential for lowering COVID-19 morbidity and mortality. This article illustrates some structural and functional relationships that may gather these drugs and the author, basing on a combined pathophysiological and pharmacological approach, recommends the FDA-approved antidiarrhea drug; nitazoxanide, which has been previously suggested but unfortunately widely ignored, to be tested in combination with azithromycin for their potential activity against SARS CoV-2, soonest. The author also recommends testing their combined administration as early during the clinical course of COVID-19 as possible. Further, basing on the same represented concept, the author suggests more trials for interferons to be tested against SARS CoV-2, especially in severe and critical COVID-19 cases.

Keywords: SARS-CoV-2; COVID-19; Antivirals; Nitazoxanide; Azithromycin.

—–

Association of #Treatment With #Hydroxychloroquine or #Azithromycin With In-Hospital #Mortality in Patients With #COVID19 in New York State (JAMA, abstract)

[Source: JAMA, full page: (LINK). Abstract, edited.]

Association of Treatment With Hydroxychloroquine or Azithromycin With In-Hospital Mortality in Patients With COVID-19 in New York State

Eli S. Rosenberg, PhD1; Elizabeth M. Dufort, MD2; Tomoko Udo, PhD1; et al. Larissa A. Wilberschied, MS2; Jessica Kumar, DO2; James Tesoriero, PhD2; Patti Weinberg, PA3; James Kirkwood, MPH2; Alison Muse, MPH2; Jack DeHovitz, MD3,4; Debra S. Blog, MD2; Brad Hutton, MPH2; David R. Holtgrave, PhD1; Howard A. Zucker, MD2

Author Affiliations: 1 University at Albany School of Public Health, State University of New York, Rensselaer; 2 New York State Department of Health, Albany; 3 IPRO, Lake  Success, New York; 4 Downstate Health Sciences University, State University of New York,  Brooklyn

JAMA. Published online May 11, 2020. doi:10.1001/jama.2020.8630

 

Key Points

  • Question  – Among patients with coronavirus disease 2019 (COVID-19), is there an association between use of hydroxychloroquine, with or without azithromycin, and in-hospital mortality?
  • Findings  – In a retrospective cohort study of 1438 patients hospitalized in metropolitan New York, compared with treatment with neither drug, the adjusted hazard ratio for in-hospital mortality for treatment with hydroxychloroquine alone was 1.08, for azithromycin alone was 0.56, and for combined hydroxychloroquine and azithromycin was 1.35. None of these hazard ratios were statistically significant.
  • Meaning  – Among patients hospitalized with COVID-19, treatment with hydroxychloroquine, azithromycin, or both was not associated with significantly lower in-hospital mortality.

 

Abstract

Importance  

Hydroxychloroquine, with or without azithromycin, has been considered as a possible therapeutic agent for patients with coronavirus disease 2019 (COVID-19). However, there are limited data on efficacy and associated adverse events.

Objective  

To describe the association between use of hydroxychloroquine, with or without azithromycin, and clinical outcomes among hospital inpatients diagnosed with COVID-19.

Design, Setting, and Participants  

Retrospective multicenter cohort study of patients from a random sample of all admitted patients with laboratory-confirmed COVID-19 in 25 hospitals, representing 88.2% of patients with COVID-19 in the New York metropolitan region. Eligible patients were admitted for at least 24 hours between March 15 and 28, 2020. Medications, preexisting conditions, clinical measures on admission, outcomes, and adverse events were abstracted from medical records. The date of final follow-up was April 24, 2020.

Exposures  

Receipt of both hydroxychloroquine and azithromycin, hydroxychloroquine alone, azithromycin alone, or neither.

Main Outcomes and Measures  

Primary outcome was in-hospital mortality. Secondary outcomes were cardiac arrest and abnormal electrocardiogram findings (arrhythmia or QT prolongation).

Results  

Among 1438 hospitalized patients with a diagnosis of COVID-19 (858 [59.7%] male, median age, 63 years), those receiving hydroxychloroquine, azithromycin, or both were more likely than those not receiving either drug to have diabetes, respiratory rate >22/min, abnormal chest imaging findings, O2 saturation lower than 90%, and aspartate aminotransferase greater than 40 U/L. Overall in-hospital mortality was 20.3% (95% CI, 18.2%-22.4%). The probability of death for patients receiving hydroxychloroquine + azithromycin was 189/735 (25.7% [95% CI, 22.3%-28.9%]), hydroxychloroquine alone, 54/271 (19.9% [95% CI, 15.2%-24.7%]), azithromycin alone, 21/211 (10.0% [95% CI, 5.9%-14.0%]), and neither drug, 28/221 (12.7% [95% CI, 8.3%-17.1%]). In adjusted Cox proportional hazards models, compared with patients receiving neither drug, there were no significant differences in mortality for patients receiving hydroxychloroquine + azithromycin (HR, 1.35 [95% CI, 0.76-2.40]), hydroxychloroquine alone (HR, 1.08 [95% CI, 0.63-1.85]), or azithromycin alone (HR, 0.56 [95% CI, 0.26-1.21]). In logistic models, compared with patients receiving neither drug cardiac arrest was significantly more likely in patients receiving hydroxychloroquine + azithromycin (adjusted OR, 2.13 [95% CI, 1.12-4.05]), but not hydroxychloroquine alone (adjusted OR, 1.91 [95% CI, 0.96-3.81]) or azithromycin alone (adjusted OR, 0.64 [95% CI, 0.27-1.56]), . In adjusted logistic regression models, there were no significant differences in the relative likelihood of abnormal electrocardiogram findings.

Conclusions and Relevance  

Among patients hospitalized in metropolitan New York with COVID-19, treatment with hydroxychloroquine, azithromycin, or both, compared with neither treatment, was not significantly associated with differences in in-hospital mortality. However, the interpretation of these findings may be limited by the observational design.

Keywords: SARS-CoV-2; COVID-19; USA; Antivirals; Chloroquine; Azithromycin.

——

Rapid #repurposing of #drugs for #COVID19 (Science, summary)

[Source: Science, full page: (LINK). Summary, edited.]

Rapid repurposing of drugs for COVID-19

R. Kiplin Guy1, Robert S. DiPaola2, Frank Romanelli1, Rebecca E. Dutch2

1 College of Pharmacy, University of Kentucky, Lexington, KY, USA. 2 College of Medicine, University of Kentucky, Lexington, KY, USA. Email: kip.guy@uky.edu

Science  08 May 2020: eabb9332 | DOI: 10.1126/science.abb9332

 

Abstract

The emergence of a new coronaviral respiratory disease calls for repurposing existing drugs

___

In late fall 2019, a novel acute respiratory disease, called coronavirus disease 2019 (COVID-19) emerged in Wuhan, China. COVID-19 is caused by severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2) (1, 2). COVID-19 has been declared a pandemic by the World Health Organization and continues to spread across the globe. Most patients recover within 1 to 3 weeks. However, a small proportion (~5%) develop severe illness that can progress to acute respiratory distress syndrome (ARDS), which can lead to death. Currently, only supportive care is available; patients would greatly benefit from the availability of direct therapeutic approaches. One approach to identifying therapeutics is to repurpose approved drugs developed for other uses, which takes advantage of existing detailed information on human pharmacology and toxicology to enable rapid clinical trials and regulatory review.

(…)

Keywords: SARS-CoV-2; COVID-19; Antivirals.

—–

#Cardiac #safety and potential efficacy: two reasons for considering #minocycline in place of #azithromycin in #COVID19 management (Eur Heart J., summary)

[Source: European Heart Journal, full page: (LINK). Summary, edited.]

Cardiac safety and potential efficacy: two reasons for considering minocycline in place of azithromycin in COVID-19 management

Giovanni Diana, Rocky Strollo, Davide Diana, Mirko Strollo, Alfredo R Galassi, Filippo Crea

European Heart Journal – Cardiovascular Pharmacotherapy,  pvaa049, https://doi.org/10.1093/ehjcvp/pvaa049

Published: 07 May 2020

Issue Section: Correspondence

___

Currently, there is no effective therapy for COVID-19, and several approaches are under investigation. Nevertheless, some drugs are used off-label despite the absence of clear data on their effectiveness. Among these, hydroxychloroquine suppresses SARS-CoV-2 replication in vitro,1 and clinical trials are ongoing to evaluate its use as an anti-COVID-19 agent. To date, the FDA and EMA allow its use only in hospitalized patients with severe COVID-19 or in those at high risk, in cases where other trials are not feasible. According to a small non-randomized study, hydroxychloroquine’s efficacy might be enhanced by azithromycin, as the combination of these two drugs appeared to accelerate viral clearance.2 However, these findings were not substantiated by another study performed in severe COVID-19 cases.3

(…)

Keywords: SARS-CoV-2; COVID-19; Antivirals; Chloroquine; Azithromycin; Minocycline; Cardiology; Drugs safety.

—–

#Virological and #clinical cure in #COVID19 patients treated with #hydroxychloroquine: A systematic review and meta‐analysis (J Med Virol., abstract)

[Source: Journal of Medical Virology, full page: (LINK). Abstract, edited.]

Virological and clinical cure in COVID‐19 patients treated with hydroxychloroquine: A systematic review and meta‐analysis

Phulen Sarma,  Hardeep Kaur,  Harish Kumar,  Dhruv Mahendru,  Pramod Avti, Anusuya Bhattacharyya,  Manisha Prajapat,  Nishant Shekhar,  Subodh Kumar,  Rahul Singh, Ashutosh Singh,  Deba Prasad Dhibar,  Ajay Prakash,  Bikash Medhi, …

First published: 16 April 2020 | DOI:  https://doi.org/10.1002/jmv.25898

Phulen Sarma and Hardeep Kaur contributed equally to this study.

 

Abstract

Following the demonstration of the efficacy of hydroxychloroquine against severe acute respiratory syndrome coronavirus 2 in vitro, many trials started to evaluate its efficacy in clinical settings. However, no systematic review and meta‐analysis have addressed the issue of the safety and efficacy of hydroxychloroquine (HCQ) in coronavirus disease 2019. We conducted a systematic review and meta‐analysis with the objectives of evaluation of safety and efficacy of HCQ alone or in combination in terms of “time to clinical cure,” “virological cure,” “death or clinical worsening of disease,” “radiological progression,” and safety. RevMan was used for meta‐analysis. We searched 16 literature databases out of which seven studies (n = 1358) were included in the systematic review. In terms of clinical cure, two studies reported possible benefit in “time to body temperature normalization” and one study reported less “cough days” in the HCQ arm. Treatment with HCQ resulted in less number of cases showing the radiological progression of lung disease (odds ratio [OR], 0.31, 95% confidence interval [CI], 0.11‐0.9). No difference was observed in virological cure (OR, 2.37, 95% CI, 0.13‐44.53), death or clinical worsening of disease (OR, 1.37, 95% CI, 1.37‐21.97), and safety (OR, 2.19, 95% CI, 0.59‐8.18), when compared with the control/conventional treatment. Five studies reported either the safety or efficacy of HCQ + azithromycin. Although seems safe and effective, more data are required for a definitive conclusion. HCQ seems to be promising in terms of less number of cases with radiological progression with a comparable safety profile to control/conventional treatment. We need more data to come to a definite conclusion.

 

Research Highlights

  • Following the demonstration of the efficacy of hydroxychloroquine (HCQ) against severe acute respiratory syndrome coronavirus 2 in vitro, many trials were started to evaluate its efficacy in clinical settings.
  • However, no systematic review and meta‐analysis have addressed the issue to the safety and efficacy of HCQ in coronavirus disease 2019 (COVID‐19).
  • We searched 16 literature databases finally seven articles were identified, which evaluated the therapeutic efficacy of HCQ either alone or in combination with azithromycin in COVID‐19.
  • RevMan was used for meta‐analysis. For continuous outcome, mean difference and for a dichotomous outcome, odds ratio with 95% confidence interval was calculated. Model selection (fixed effect or random effect) was done on the basis of heterogeneity among different studies.
  • Three studies reported the safety and efficacy of HCQ vs control/conventional treatment in terms of safety and efficacy in COVID‐19.
  • Treatment with HCQ resulted in benefit in terms of less number of cases with radiological progression with no increase in adverse events when compared with control/conventional/standard treatment.
  • We can also expect a benefit in terms of a number of days to body temperature normalization and number of cough days.
  • However, at this current point of time, no difference was seen in terms of virological cure on day 6 to 7 postinitiation of therapy and composite death or worsening of the disease.
  • Four studies reported efficacy and five studies reported safety of the HCQ + azithromycin combination (out of which three studies from the same group).
  • Although the combination of HCQ + azithromycin seems to be effective and safe, we need more controlled studies to come to an effective conclusion. However, electrocardiographic monitoring is essential while using this combination due to the risk of QT prolongation.

Keywords: SARS-CoV-2; COVID-19; Antivirals; Chloroquine; Azithromycin.

—–