Currently, SARS-CoV-2 infection which is the causative agent for COVID-19 disease is a worldwide pandemic with more than 100 million global cases and more than 2.0 million deaths (as of January, 2021). While several vaccines for prevention of COVID-19 have already been registered by the regulatory authorities, the problem is that the substitution rate of this virus is estimated to be one change per 2 weeks, thus mutations could arise that threaten the efficacy of vaccines. Unfortunately, there is no current evidence from random clinical trials to recommend any specific post-exposure treatment for patients with suspected or confirmed COVID-19 disease. Here we propose an innovative superinfection therapeutic (SIT) strategy, which could complement the development of prophylactic vaccines. SIT is based on clinical observations that unrelated harmless viruses might interact in patients infected with pathogenic virus. During SIT, the patient benefits from superinfection with an apathogenic double-stranded RNA (dsRNA) virus such as the infectious bursal disease virus (IBDV), which is a powerful activator of the interferon-dependent antiviral gene program. An attenuated vaccine strain of IBDV was already successfully administered to resolve acute and persistent infections induced by two completely different viruses, the hepatitis B (DNA) and C (RNA) viruses (HBV/HCV). The safety of orally administered acid-resistant IBDV strain R903/78 reverse engineered viral drug candidate was demonstrated in 10 stage IV cancer patients who exhausted all conventional therapy. Following repeated oral administration of the virus up to 109 infectious units (IU)/ dose, only mild flu-like side effects were reported in some patients. Proof-of-principle efficacy was demonstrated in an early COVID-19 patient who was successfully treated with 3x106 IU of an attenuated IBDV vaccine. A small scale dose-finding Phase I safety study is proposed.

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Stochastic simulations of early outbreak trajectories found that the basic reproduction number, R0, of the Wuhan new coronavirus (2019-nCoV) is around 2.2, which indicates the potential for sustained human-to-human transmission. In fact, this transmission characteristic is a similar magnitude to severe acute respiratory syndrome-related coronavirus (SARS-CoV) and the 1918 pandemic influenza. Cases have now spread to at least 4 continents, currently with 43,108 cases and 1,018 lives lost. The World Health Organization (WHO) declared the outbreak a public health emergency of international concern. There is no current evidence from random clinical trials (RCTs) to recommend any specific anti-nCoV treatment for patients with suspected or confirmed 2019-nCoV infection. In order to mitigate the impact of the 2019-nCoV outbreak, here we propose an innovative superinfection therapeutic (SIT) strategy, which could complement the development of prophylactic vaccines. SIT is based on clinical observations that unrelated viruses might interact in co-infected patients. During SIT, the patient benefit from superinfection with an apathogenic dsRNA virus such as the infectious bursal disease virus (IBDV), which is a powerful activator of the interferon-dependent antiviral gene program. An attenuated vaccine strain of IBDV was already successfully administered to resolve acute and persistent infections induced by two completely different viruses, the hepatitis B (DNA) and C (RNA) viruses (HBV/HCV). Importantly, IBDV is also a potential prophylactic vaccine vector drug candidate, since a recombinant IBDV was previously generated that displays exogenous viral peptides from a replication-competent IBDV.