Case report: Clearance of longstanding, immune-deficiency-associated, vaccine-derived polio virus infection following remdesivir therapy for chronic SARS-CoV-2 infection

Abstract

The global polio eradication campaign has had remarkable success in reducing wild-type poliovirus infection, largely built upon the live attenuated Sabin oral poliovirus vaccine. Whilst rare, vaccine poliovirus strains may cause infection and subsequently revert to a neurovirulent type, termed vaccine-derived poliovirus (VDPV). Persistent, vaccine derived infection may occur in an immunocompromised host (iVDPV), where it is a recognised complication following receipt of the Sabin vaccine. This has significant implications for the global polio eradication campaign and there is currently no agreed global strategy to manage such patients.Here we describe a case of a 50-year-old man with common variable immune deficiency, persistently infected with a neurovirulent vaccine-derived type 2 poliovirus following vaccination in childhood. iVDPV infection had proven resistant to multiple prior attempts at treatment with human breast milk, ribavirin and oral administration of a normal human pooled immunoglobulin product. His iVDPV infection subsequently resolved after 12 days treatment with remdesivir, an adenosine analogue prodrug that is an inhibitor of viral RNA-dependent RNA polymerase, administered as treatment for a prolonged, moderate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. iVDPV from the patient, isolated prior to treatment, was subsequently demonstrated to be sensitive to remdesivir in vitro. Based on the observations made in this case, and the mechanistic rationale for use with iVDPV, there is strong justification for further clinical studies of remdesivir treatment as a potentially curative intervention in patients with iVDPV infection.

Health Economic Analysis of Antiviral Drugs in the Global Polio Eradication Endgame

“…Interestingly, a known, long-term (>30 years) chronic excreter appears to have stopped excreting polioviruses after COVID-19 infection and Paxlovid ™ treatment, but uncertainty remains about whether COVID-19 infection or the antiviral drug led to the end of poliovirus infection in this individual. 63 Generally, the regulatory path to approval of a specific PAVD continues to prove more challenging than might occur with the potential off-label use or repurposing of an existing antiviral or anti-enteroviral drug. The compassionate use of PAVDs for individual iVDPV excreters could potentially continue as part of studies of investigational new drugs, or could come under consideration as orphan drugs (i.e., pharmaceutical products for which insufficient markets exist to support their commercial use).…”

The multiple roles of viral 3D pol protein in picornavirus infections

“…Recent studies have identified that GS-5734 inhibits RNA synthesis of EV-A71, hindering enterovirus replication, and shows broad-spectrum inhibition of a wide range of enteroviruses [ 100 ]. Similarly, current clinical data showed that vaccine-derived poliovirus infection in an immunocompromised patient was cured by GS-5734 treatment after multiple failed attempts to treat with human milk, ribavirin, and oral human immunoglobulin [ 101 ].…”

The Fight against Poliovirus Is Not Over

“…A recent study reported that remdesivir treatment eliminated iVDPV in the stool of a 50-year-old patient. These results suggest that remdesivir may be effective in the treatment of iVDPV [ 139 ].…”