For the LoVE of SARS-CoV-2: From Long COVID to Viral Evasion and Rebound
Long COVID, or post-acute sequelae of SARS-CoV-2, continues to remain a mystery in the medical field, and was a key topic of discussion at CROI. In line with that, Shionogi presented promising six-month data from a Phase 2/3 study that suggested treatment with its oral antiviral, ensitrelvir, of mild-to-moderate SARS-CoV-2 infection could potentially reduce the risk of developing long COVID in standard-risk patients.
Symptomatic and/or virological rebound was another topic of interest at CROI. While the phenomenon first gained public interest in the context of rebound after Pfizer’s Paxlovid treatment, it is also observed in untreated COVID-19 patients, as well as in patients who received COVID-19 monoclonal antibody (mAb) therapy. Viral rebound is a particular concern in the immunocompromised population, further exacerbated by the ongoing viral drift of SARS-CoV-2, which has led to limited treatment and prophylactic options for these patients. Antivirals are currently used in these immunocompromised patients, nonetheless, new preventive options are still highly sought-after since vaccines are not an optimal preventive solution in this risk population. Novel pan-sarbecovirus and COVID-19 mAbs targeting functionally constrained regions on the spike protein, as well as ACE2-targeting mAbs, may present new preventative solutions in the light of variants of concern.
However, with COVID-19 variants continuing to evolve and no end in sight for COVID-19 outbreaks, regulators may need to consider implementing specific accelerated approval pathways for COVID-19 mAbs to ensure preventive options for the most vulnerable populations are available. While still an unresolved mystery, the inclusion of long COVID outcome measures into pivotal antiviral studies could also become increasingly attractive to developers, although it remains to be seen how Shionogi’s ensitrelvir may be adopted as a strategy against long COVID. Prevention or reduction of long-COVID could become a driver for the prescription or measure for longer-term cost-effectiveness of COVID-19 therapeutic, potentially presenting a differentiator in the growing antiviral market.