COMBINATION ANTIVIRAL THERAPY
Rapid and amplified viral replication is the hallmark of most acute viral infections. By reducing the rate, quantity, or duration of viral replication, the degree of direct viral injury to the respiratory epithelium, vasculature, and organs may be lessened.16 Additionally, secondary processes that depend on viral stimulation, including the activation of inflammatory cells, cytokines, and coagulation, could potentially be lessened if viral replication is attenuated. Because no form of readily available medication has been designed specifically to inhibit SARS-CoV-2 replication, 2 or more of the nonspecific agents listed here can be entertained. None of the approaches listed have specific regulatory approved advertising labels for their manufacturers; thus all would be appropriately considered acceptable “off-label” use.17
Zinc Lozenges and Zinc Sulfate
Zinc is a known inhibitor of coronavirus replication. Clinical trials of zinc lozenges in the common cold have demonstrated modest reductions in the duration and or severity of symptoms.18 By extension, this readily available nontoxic therapy could be deployed at the first signs of COVID-19.19 Zinc lozenges can be administered 5 times a day for up to 5 days and extended if needed if symptoms persist. The amount of elemental zinc lozenges is less than 25% of that in a single 220-mg zinc sulfate daily tablet. This dose of zinc sulfate has been effectively used in combination with antimalarials in early treatment of high-risk outpatients with COVID-19.20
Antimalarials
Hydroxychloroquine (HCQ) is an antimalarial/anti-inflammatory drug that impairs endosomal transfer of virions within human cells. HCQ is also a zinc ionophore that conveys zinc intracellularly to block the SARS-CoV-2 RNA-dependent RNA polymerase, which is the coreenzyme of the virus replication.21 The currently completed retrospective studies and randomized trials have generally shown these findings: 1) when started late in the hospital course and for short durations of time, antimalarials appear to be ineffective, 2) when started earlier in the hospital course, for progressively longer durations and in outpatients, antimalarials may reduce the progression of disease, prevent hospitalization, and are associated with reduced mortality.22−25 In a retrospective inpatient study of 2541 patients hospitalized with COVID-19, therapy associated with an adjusted reduction in mortality was HCQ alone (hazard ratio [HR] = 0.34, 95% confidence interval [CI] 0.25-0.46,P<0.001) and HCQ with azithromycin (HR = 0.29, 95% CI 0.22-0.40,P<0.001).23HCQ was approved by the US Food and Drug Administration in 1955, has been used by hundreds of millions of people worldwide since then, is sold over the counter in many countries, and has a well-characterized safety profile that should not raise undue alarm.25,26 Although asymptomatic QT prolongation is a well-recognized and infrequent (<1%)complication of HCQ, it is possible that in the setting of acute illness symptomatic arrhythmias could develop. Data safety and monitoring boards have not declared safety concerns in any clinical trial published to date. Rare patients with a personal or family history of prolonged QT syndrome and those on additional QT prolonging, contraindicated drugs (eg, dofetilide, sotalol) should be treated with caution and a plan to monitor the QTc in the ambulatory setting. A typical HCQ regimen is 200 mg bid for 5 days and extended to 30 days for continued symptoms. A minimal sufficient dose of HCQ should be used, because inexcessive doses the drug can interfere with early immune response to the virus.
Azithromycin…
Doxycycline…
Favipiravir…
Read more and see references at https://www.amjmed.com/article/S0002-9343(20)30673-2/pdf
