Effective approaches to disaster evacuation during a COVID-like pandemic (preprint)

Since COVID-19 vaccines became available, no studies have quantified how different disaster evacuation strategies can mitigate pandemic risks in shelters. Therefore, we applied an age-structured epidemiological model, known as the Susceptible-Exposed-Infectious-Recovered (SEIR) model, to investigate to what extent different vaccine uptake levels and the Diversion protocol implemented in Taiwan decrease infections and delay pandemic peak occurrences. Taiwan's Diversion protocol involves diverting those in self-quarantine due to exposure, thus preventing them from mingling with the general public at a congregate shelter. The Diversion protocol, combined with sufficient vaccine uptake, can decrease the maximum number of infections and delay outbreaks relative to scenarios without such strategies. When the diversion of all exposed people is not possible, or vaccine uptake is insufficient, the Diversion protocol is still valuable. Furthermore, a group of evacuees that consists primarily of a young adult population tends to experience pandemic peak occurrences sooner and have up to 180% more infections than does a majority elderly group when the Diversion protocol is implemented. However, when the Diversion protocol is not enforced, the majority elderly group suffers from up to 20% more severe cases than the majority young adult group.

Testing and Quarantine Strategies for Travelers – An Evidence Based Analytic Model Using Bayesʼ Theorem (preprint)

Background: Policies such as border closures and quarantines have been widely used to minimize the spread of SARS-CoV-2 during the COVID-19 pandemic. However, such policies curbed international trade, travel, and tourism, leading to economic loss. Methods: We calculated the risks of individual travelers based on their expected transmission, defined as the expected number of subsequent infections resulting from an individual. It is calculated by multiplying the probability of travelers having COVID-19 after negative test(s), with the effective reproduction number (Rt) of the viral strain/variant. The expected transmission varies based on the incidence rate among unvaccinated or the breakthrough infection rates (BIRs) of the vaccinated; waning vaccine efficacy; transmissibility of the dominant variants; properties of various diagnostic tests used; and restriction policies in the arrival countries. For a traveler to be released, the expected transmission was benchmarked against that of an unvaccinated traveler quarantined for 14 days without testing, previously calculated to be 0.005. Results: We found that all individuals with a negative preboarding test can be released with a negative post-arrival test, with both tests achieving sensitivity ≥ 90% and specificity ≥ 97%, which could be accomplished by rapid antigen tests. This is valid for an incidence rate up to 0.1 (prior to testing) and Rt up to 4 in the arrival country. In a sensitivity analysis scenario where the incidence rate is 0.4 and Rt is 16, a negative preboarding test and a negative post-arrival test, both with sensitivity ≥ 98% and specificity ≥ 97% (usually accomplished by a Polymerase Chain Reaction test or other Nucleic Acid Amplification tests) can ensure that a traveler has a lower expected transmission than an unvaccinated person who is quarantined for 14 days. Conclusions: As vaccines become more available around the world, this study provides the scientific basis for setting policies of testing with or without quarantine for international travelers. In many cases, travelers with full vaccination (with or without booster) and a negative preboarding test can be released with a negative rapid antigen test upon arrival, which will allow the travelers to depart the airport within 30 minutes.

A Novel SARS-CoV-2 Multitope Protein/Peptide Vaccine Candidate is Highly Immunogenic and Prevents Lung Infection in an Adeno Associated Virus Human Angiotensin-Converting Enzyme 2 (AAV hACE2) Mouse Model (preprint)

In this report, we describe the initial development and proof-of-concept studies for UB-612, the first multitope protein-peptide vaccine against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the pathogen responsible for the Coronavirus Disease of 2019 (COVID-19). UB-612 consists of eight components rationally designed for induction of high neutralizing antibodies and broad T cell responses against SARS-CoV-2: the S1-RBD-sFc fusion protein, six synthetic peptides (one universal peptide and five SARS-CoV-2-derived peptides), a proprietary CpG TLR-9 agonist, and aluminum phosphate adjuvant. Through immunogenicity studies in guinea pigs and rats, we optimized the design of protein/peptide immunogens and selected an adjuvant system, yielding a vaccine that provided excellent S1-RBD binding and high neutralizing antibody responses, robust cellular responses, and a Th1-oriented response at low doses of the vaccine. Our candidate vaccine was then advanced into challenge studies, in which it reduced viral load and prevented development of disease in a mouse challenge model and in nonhuman primates (NHP, immunogenicity part is completed, challenge is ongoing). A GLP-compliant toxicity study has shown a favorable safety profile for the vaccine. With the Phase 1 trial ongoing in Taiwan and additional trials planned worldwide, UB-612 is a highly promising and differentiated vaccine candidate for prevention of SARS-CoV-2 transmission and COVID-19 disease.

Emetine as an antiviral agent suppresses SARS-CoV-2 replication by inhibiting interaction of viral mRNA with eIF4E: An in vitro study (preprint)

Emetine is a FDA-approved drug for the treatment of amebiasis. In the recent times we had also demonstrated the antiviral efficacy of emetine against some RNA and DNA viruses. Following emergence of the COVID-19, we further evaluated the in vitro antiviral activity of emetine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The therapeutic index of emetine was determined to be 10910.4, at a cytotoxic concentration 50 (CC50) of 1603.8 nM and effective concentration 50 (EC50) of 0.147 nM. Besides, we also demonstrated the protective efficacy of emetine against lethal challenge with infectious bronchitis virus (IBV; a chicken coronavirus) in the embryonated chicken egg infection model. Emetine treatment was shown to decrease viral RNA and protein synthesis without affecting other steps of viral life cycle such as attachment, entry and budding. In a chromatin immunoprecipitation (CHIP) assay, emetine was shown to disrupt the binding of SARS-CoV-2 RNA with eIF4E (eukaryotic translation initiation factor 4E, a cellular cap-binding protein required for initiation of protein translation). Further, SARS-CoV-2 was shown to exploit ERK/MNK1/eIF4E signalling pathway for its effective replication in the target cells. To conclude, emetine targets SARS-CoV-2 protein synthesis which is mediated via inhibiting the interaction of SARS-CoV-2 RNA with eIF4E. This is a novel mechanistic insight on the antiviral efficacy of emetine. In vitro antiviral efficacy against SARS-CoV-2 and its ability to protect chicken embryos against IBV suggests that emetine could be repurposed to treat COVID-19.