Finding Novel Therapies for COVID-19

Volume 23, Issue 3

As reported in last week’s Talking Therapeutics column, the SARS-CoV-2 virus is continuing to develop mutations which render our vaccines less effective at preventing infection. This is especially true of the new XBB.1 and BQ.1.1 variants, which can even easily evade the new bivalent boosters that were deployed last fall.

Given the ongoing threat of COVID-19 infection, the search for novel therapies to fight off this virus has continued. This search is even more urgent in light of the loss of monoclonal antibody products, which are no longer effective against the contemporary strains of SARS-CoV-2. Most of the focus is on dedicated antiviral treatments like nirmatrelvir/ritonavir (Paxlovid) and remdesivir (Veklury); however, non-antiviral medications may also have utility in treating COVID-19 infection.

In this week’s issue of Talking Therapeutics, we explore 2 new non-antiviral therapies that were recently studied in patients with COVID-19 infection.

Point 1: Promise for PCSK9 Inhibitors

Vascular inflammation is a hallmark feature of patients with severe COVID-19 infection, and PCSK9 inhibitors have potent anti-inflammatory properties. In a small pilot study of 60 patients admitted to the hospital with severe COVID-19, those randomized to a single, 140-mg dose of evolocumab had lower rates of death or intubation within 30 days vs placebo (23.3% vs 53.3%, risk difference: -30%; 95% CI: -53.40% to -6.59%). Additionally, serum levels of IL-6, a key inflammatory mediator, were lower in the evolocumab cohort, and patients with higher baseline levels of IL-6 derived a larger benefit with evolocumab therapy.

As this is only a pilot study, these results should be confirmed in a larger trial before practitioners recommend a PCSK9 inhibitor to those with severe COVID-19 infection. Nevertheless, given the relative safety and low cost of a single dose of evolocumab, this therapy shows tremendous promise based on this limited dataset.

Point 2: No Benefit From Fluvoxamine

Fluvoxamine is a selective serotonin reuptake inhibitor and antidepressant with a purported mechanism of action against the COVID-19 virus. In a recent issue of the Journal of the American Medical Association, a large randomized trial was published comparing fluvoxamine, administered at a dosage of 50 mg twice daily for 10 days, against placebo in a cohort of outpatients with mild to moderate COVID-19.

The primary outcome, time to sustained recovery (defined as the third day of 3 consecutive days without symptoms), occurred with similar frequency in both groups. This indicates fluvoxamine is not effective against mild to moderate COVID-19 infection at this dose and duration.