This trial is evaluating whether [18F]F-AraG (2'-deoxy-2'-fluoro-9-β-D-arabinofuranosylguanine) will improve 1 primary outcome and 3 secondary outcomes in patients with COVID-19. Measurement will happen over the course of 4 weeks.
This trial requires 20 total participants across 2 different treatment groups
This trial involves 2 different treatments. [18F]F-AraG (2'-deoxy-2'-fluoro-9-β-D-arabinofuranosylguanine) is the primary treatment being studied. Participants will all receive the same treatment. There is no placebo group. The treatments being tested are in Phase < 1 and are in the first stage of evaluation with people.
The symptoms of Covid-19 have not changed very much since the SARS outbreak because people had developed cross immunity against the virus due to prior exposure. The symptoms are the same as in the initial stages of SARS. The most common symptoms of the disease are fever, cough, and shortness of breath. Some patients have presented with a headache along with the same symptoms. This is very common in the SARS outbreak. The incubation period of coronaviruses is three to seven days and is different between the two strains of coronaviruses. Most people are in the incubation period, but it goes into remission in some. Only half of the patient will develop full-blown pneumonia.
Many factors contribute to the spread of the disease, including human-to-human transmission of the virus, contact between infected people and unaffected people; the way in which the virus can be spread among people; and the virus mutations. Further studies are needed to elucidate the mechanisms underlying it.
Covid-19 (COVID-19) is an influenza-like illness that is caused by an infectious virus in the same family as influenza and has no known treatment. Approximately 1% of cases evolve into severe disease, defined by a sudden increase in severity of symptoms. In Hong Kong, there were 1184 confirmed cases and 19 deaths by 16 March. The cause of death was commonly respiratory disease.
An estimated 494 million Americans will acquire a case of acute respiratory infection; 9.0 million will die. It will be the largest U.S. outbreak in modern history.
Some patients are benefiting from antiviral agents, antibiotics and other treatment. But since it is a novel infectious disease people who are not recovered from pneumonia could fall back into a worse condition and may eventually die.
f-AraG did not appear to provide a superior reduction in tumor volume in the treatment arm for either the complete or partial responders compared with any placebo on a two-week, three-cycle course plus 7 days of rest for either study. Given the similar outcomes among complete, partial and non-responders, it is difficult to conclude that f-AraG is more effective than the placebo when all treatment arms are included.
Recent findings, [18f]fluoro-GMP can be rapidly and non-invasively quantified in vivo; (18)f-arag shows promise as a potential PET or SPECT radiotracer for detecting non-small cell lung cancers expressing f-CGR.
The side effects of [18f]-araG in the current clinical formulation are as follows.\n\nAra-G is rapidly and selectively taken up by the cell's nucleus where it binds to one or a family of DNA repair proteins. It interferes with DNA polymerase function for at least 11 weeks, blocking replication and repair of DNA damaged by carcinogens and genotoxic compounds. In the case of ara-G, the blocking effect was reversible because the DNA repair and replication process were restored after discontinuing treatment. The side effects of Ara-G were due, in part, to its induction of cell toxicity, because Ara-G bound to DNA repair proteins and stalled replication forks.
(18)F-arag appears very promising to diagnose and inactivate the virus if used as radiolabel. It also appears promising for assessing virus load in plasma by PET after the administration of (18)F-arag. All in all, these studies may help guide the choices of the best radiolabel for the next generation of diagnostic and therapeutic tools. For other cancer types, they will only provide a clue for further research rather than guiding the final decision but still could add to our understanding of the nature of the virus. (18)F-arag is also very promising for inactivation and tracking of the virus in infected animals.
F-AG is used in combination with a wide range of chemotherapy. It seems that F-AG is less toxic when used in the same way. However F-AG can sometimes alter the plasma pharmacokinetic behaviour of the other chemoradiosensitising drugs used commonly in combination with cisplatin. This is not yet fully understood, but might be a consequence of binding the free cisplatin to F-AG while simultaneously inhibiting the cellular uptake of cisplatin.
The data suggest the virus was likely brought to Asia first by a visitor, who then transported the virus to East and Southeast Asia through its migration from China. When East and Southeast Asia infected the West, the virus spread easily from travelers to the local population, and also from the local population to the healthcare personnel with close contact with travelers. This may explain that the virus was transmitted to many countries very quickly. This spread was mainly brought by air travel and tourism. Although most cases were reported in hospitals (95%), the majority (86%) were not imported from any country.