Preprint Hypothesis Version 4 Preserved in Portico This version is not peer-reviewed

The clinically validated viral superinfection therapy (SIT) platform technology could cure early cases of COVID-19 disease

Version 1 : Received: 11 February 2020 / Approved: 11 February 2020 / Online: 11 February 2020 (11:54:03 CET)
Version 2 : Received: 4 March 2020 / Approved: 4 March 2020 / Online: 4 March 2020 (11:08:41 CET)
Version 3 : Received: 19 March 2020 / Approved: 20 March 2020 / Online: 20 March 2020 (09:31:54 CET)
Version 4 : Received: 27 January 2021 / Approved: 1 February 2021 / Online: 1 February 2021 (16:07:55 CET)

How to cite: Kovesdi, I.; Sandig, V.; Slavin, S.; Renz, W.; Ranst, M.V.; Chumakov, P.M.; Bakács, T. The clinically validated viral superinfection therapy (SIT) platform technology could cure early cases of COVID-19 disease. Preprints 2020, 2020020147 (doi: 10.20944/preprints202002.0147.v4). Kovesdi, I.; Sandig, V.; Slavin, S.; Renz, W.; Ranst, M.V.; Chumakov, P.M.; Bakács, T. The clinically validated viral superinfection therapy (SIT) platform technology could cure early cases of COVID-19 disease. Preprints 2020, 2020020147 (doi: 10.20944/preprints202002.0147.v4).

Abstract

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.

Subject Areas

Coronavirus; SARS-CoV-2; COVID-19; interferon; IFN; superinfection therapy; SIT; infectious bursal disease virus; IBDV; R903/78; safety; treatment

Comments (1)

Comment 1
Received: 1 February 2021
Commenter: Tibor Bakacs
Commenter's Conflict of Interests: Author
Comment: We have obtained in vitro data concerning the mechanism of action of our IBDV R903/78 drug candidate. R903/78 strongly induces IFN-beta in A549 cells infected for 32 h with R903/78 at MOI=1 (about 30x) and IFN-lambda (5-10x). As IFN alpha treatment reduces SARS-CoV-2 titers by 3-4 orders of magnitude our results indicate that the interferon activation properties of R903/78 are promising to counter SARS-CoV-2 virus infections. More importantly, we have obtained in vivo safety and efficacy results. The safety of the R903/78 virus was tested in 10 stage IV cancer patients with different type of cancers. Oral R903/78 viral treatment started with a dose of 106 IU/ dose. Then, increments from 106 to 107 to 108 and to 109 IU/ dose were orally administered. Each dose was given a week apart in order to monitor patients for potential side effects. It was reassuring that even very high doses of R903/78 virus (109 IU/dose) were associated with only mild flu-like side effects, which occurred usually 2-3 days after treatment and completely disappeared by day 5. Most importantly, we have conducted a proof-of-principle study of the R903/78 viral superinfection treatment in an early PCR positive COVID-19 male patient (43 yrs.) with mild symptoms (headaches, muscle pains, shivering, tiredness, and loss of smell). Following three days of oral treatment with 106 IU/ day of an attenuated IBDV vaccine virus all symptoms disappeared. Even the sense of smell has returned. IBDV neutralizing antibodies were demonstrated confirming the results obtained in an animal model that following oral administration of IBDV neutralizing antibodies were induced. To our best knowledge, this is the first early COVID-19 patient with mild symptoms who was successfully treated by IBDV superinfection therapy.
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