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Convalescent plasma, Remdesivir, Chloroquine and hydroxychloroquine: mechanisms of action, current status, effectiveness and side effects.
At this time, no specific drugs or therapies have been proven effective for prevention or treatment of COVID-19. Current disease management is supportive care, including supplemental oxygen and mechanical ventilator when indicated.
However, several possible treatment options are under intensive investigations:
Convalescent plasma: when someone is infected with SARS-CoV-2, the coronavirus that causes COVID-19, their immune system produces antibodies to fight the virus. People with healthy immune systems produce enough antibodies to fight the disease and recover, while those with compromised immune systems may struggle. Antibodies from blood plasma of recovered patients can be given to people with active illness to help neutralize the virus. This approach has been used in the past for some other diseases, with varying success. Studies are underway to determine its effectiveness in COVID-19, and if convalescent plasma is best used to prevent infections in high-risk individuals; to prevent mild infections from becoming severe; or to improve recovery in severely ill patients. The FDA has allowed emergency use of convalescent plasma in patients with serious or immediately life-threatening COVID-19 infections. While the treatment concept is simple, the process involves multiple steps, from selecting donors, to collecting, processing blood and safety screening. On average, plasma from one donor is only enough to treat 1 to 3 patients. For these reasons, convalescent plasma is considered a temporary solution while antiviral drugs and vaccines are developed.
Remdesivir is an antiviral drug originally created by Gilead Sciences to fight Ebola virus, but it was proved effective in treating SARS and MERS coronaviruses in laboratory and animal research. Recent studies show that Remdesivir inhibits SARS-CoV-2 infections in cultured cells, and efficiently prevents COVID-19 disease progression in monkeys. Remdesivir is an adenosine nucleotide analogue. During viral RNA synthesis, it incorporates into the nascent RNA and causes premature termination, thus interrupting viral RNA production. There are currently 6 ongoing clinical studies, some of which are large-scale phase 3 trials; and initial results are encouraging. However, as an experimental drug, Remdesivir is not expected to be available in large amounts very soon.
Chloroquine and its derivative hydroxychloroquine had recently made headlines thanks to early reports from China and France about its effectiveness in treating severely ill COVID-19 patients. Having been used to treat malaria and some autoimmune diseases, these drugs are readily available. In laboratory studies, the drugs have been shown to block entry of the virus by interfering with host cell receptor. In addition, they also inhibit virus/host cell fusion, preventing the release of viral nucleocapsid. However, more recent human studies suggest that these drugs may produce serious side effects that can be fatal. Specifically, they may cause QT interval prolongation, an abnormal heart rhythm that can quickly develop into lethal rhythms of ventricular tachycardia and fibrillation. The FDA now recommends against taking chloroquine or hydroxychloroquine for COVID-19 infections unless they are prescribed in hospitals under close supervision, or as part of a clinical trial.
