Rumor:
Combination of Hydroxychloroquine Azithromycin and Zinc Sulfate Effective in Treating Neocoronavirus Pneumonia
American medical experts say hydroxychloroquine + azithromycin + zinc sulfate treats patients with neocoronavirus infections during milder stages of the disease.
Scientific interpretation:
American time on March 28, 2020, the United States, New York doctor Vladimir Zelenko published clinical application: hydroxychloroquine, azithromycin and zinc sulfate combined application successfully cured 350 COVID-19 patients, the success rate is 100%. The efficacy of the combination of hydroxychloroquine, azithromycin and zinc sulfate on COVID-19 has been discussed controversially for a while. So can the combination of hydroxychloroquine, azithromycin and zinc sulfate effectively treat patients with mild neocoronaryngitis, or not?
1. Hydroxychloroquine
When talking about hydroxychloroquine, chloroquine needs to be mentioned first. Chloroquine is widely used in anti-malaria and autoimmune diseases, both broad-spectrum antiviral effect, which plays a direct antiviral effect by changing the intracellular PH value, inhibiting the replication of viruses dependent on pH. Chloroquine has been shown to inhibit the replication of viruses such as dengue virus, Zika virus and HIV. In addition, chloroquine can effectively block SARS-CoV infection in cell lines. The National Health Commission recommended chloroquine phosphate for the treatment of patients with COVID-19 in the Diagnostic and Treatment Program for Novel Coronavirus Pneumonia (Trial Sixth Edition), and updated its use in the Seventh Edition of the Diagnostic and Treatment Program.
Hydroxychloroquine sulfate, which adds a hydroxyl group to chloroquine, has comparable efficacy to chloroquine with lower toxicity, and is one of the potentially effective drugs for COVID-19. Zhang Qian et al. enrolled 20 patients with neocoronaryngitis in the "hydroxychloroquine+basic treatment group" and found that the clinical symptoms of the patients improved significantly in 1-2 days after treatment with hydroxychloroquine. The results of this clinical trial initially confirmed the short-term efficacy of hydroxychloroquine in the treatment of neocoronaryngitis in relieving symptoms, reversing the rate of severe disease and shortening the course of the disease. Dr. Jun Chen et al. collected 30 patients diagnosed with common type COVID-19 for a single-center, prospective, randomized and open study, and found that the prognosis of common type COVID-19 patients with hydroxychloroquine was better. However, it is difficult to compare the efficacy of the drugs in a study that uses the rate of viral turnover and the rate of re-conditioning as the primary endpoints, and subsequent studies need to identify more appropriate populations and endpoint events, and fully consider the feasibility of trials such as sample size.
Notably, studies have shown severe retinopathy and potential cardiotoxicity with prolonged heavy use of hydroxychloroquine. In addition, hydroxychloroquine is indicated for immune system disorders, and its suppressive effects on the immune system should be adequately considered when treating patients with neocoronaryngitis.
Despite the U.S. FDA issuing an emergency authorization on March 29, 2020 to allow hydroxychloroquine to be used for the treatment of COVID-19, authorities such as the U.S. FDA, the U.S. CDC (Centers for Disease Control and Prevention), and the WHO have concluded that hydroxychloroquine's effects on the neocoronavirus have yet to be studied in depth, and that the drug carries a risk of serious side effects, and that it should not be used as a potent drug, and that its self-administered use is not recommended. On April 10, the French Medicines Safety Agency also warned about the side effects of taking hydroxychloroquine for the treatment of neocoronavirus pneumonia, and in particular to be alert to the adverse effects of hydroxychloroquine on the heart. Therefore, the use of hydroxychloroquine for the treatment of neocoronaryngitis should be done with great caution.
2, azithromycin
Azithromycin is a second-generation macrolide antibiotic, mainly inhibit ribonucleic acid (RNA)-dependent directional protein synthesis, thus impeding the process of bacterial trans-peptide, to achieve the effect of bacterial inhibition. Some studies have shown that azithromycin also has anti-inflammatory and immunomodulatory effects, and can be used as an adjunctive therapy in a number of infectious or non-infectious diseases. Therefore, azithromycin can play a certain therapeutic and adjunctive therapeutic role if the new coronavirus-infected person is immunocompromised or if multiple infections of gram-positive cocci, mycoplasma, chlamydia, and Legionella pneumophila are present at the same time.
Azithromycin has also been shown to have in vitro antiviral activity against SARS-CoV-2, but the mechanism of this is not clear, and may be related to the fact that azithromycin can change the pH of ribosomes or lysosomes and inhibit pH-dependent viral replication. This mechanism is similar to the antiviral mechanism of hydroxychloroquine, so the combination of azithromycin and hydroxychloroquine may have a complementary effect in antiviral. However, more studies are needed to verify this.
3, zinc sulfate
Zinc is involved in the synthesis and activation of a variety of enzymes, the synthesis of proteins, nucleic acids, intestinal protein absorption and digestion play an important physiological function. Zinc sulfate is mainly used for various diseases caused by zinc deficiency. Early studies have shown that zinc ions have ex vivo and in vivo antiviral effects, which can inhibit the replication of human rhinovirus, respiratory syncytial virus, and HIV-1, etc. Another study showed that chloroquine can promote the transport of zinc ions to the cell, so hydroxychloroquine is very likely to have the same effect. Whether azithromycin has a similar effect remains to be studied.
So when azithromycin, hydroxychloroquine, and zinc sulfate are used in combination to treat patients with neocoronaryngitis, there may be a combined antiviral effect. However, this effect needs to be confirmed by more in-depth studies.
On March 20, 2020, Didier, a French scientist, published a paper in the International Journal of Antimicrobial Agents arguing for the effectiveness of the combination of hydroxychloroquine and azithromycin in the treatment of COVID-19. But on April 3, the International Society for Antimicrobial Biochemistry said it was withdrawing the paper in question because the results of a nonrandomized clinical trial of hydroxychloroquine and azithromycin for the treatment of C. neoformans did not meet the industry's standards of *** knowledge.
In summary, there is no specific drug for Croup, and the efficacy and safety of hydroxychloroquine, azithromycin, and zinc sulfate in combination for COVID-19 remain to be confirmed in more randomized controlled clinical trials with large samples and scientifically sound experimental designs.
Discrediting expert: Wang Yu, Pharmacist-in-Charge, Qilu Children's Hospital, Shandong University
Reviewing expert: Wu Xuexin, Pharmacist-in-Charge, Qilu Children's Hospital, Shandong University
References:
1. Chen Jun, Liu Danping, Liu Li, Liu Ping, Xu Qingnian, Xia Lu, Ling Yun, Huang Dan, Song Shuli, Zhang DanDan, Qian Zhiping, Li Tao, Shen YinZhong, Lu Hongzhou. A preliminary study of hydroxychloroquine sulfate for the treatment of patients with common type 2019 coronavirus disease (COVID-19). Journal of Zhejiang University (Medical Edition).
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2. Zhang Sailong, Miao Chaoyu. Pharmacological properties of chloroquine and hydroxychloroquine and therapeutic application of new coronavirus pneumonia (COVID-19)[J/OL]. Chinese Journal of Pharmacology and Toxicology.
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