ជំងឺកូរ៉ូណាវីរុស២០១៩: ការស្រាវជ្រាវ

ការស្រាវជ្រាវ

No medication or vaccine is approved to treat the disease. International research on vaccines and medicines in COVID‑19 is underway by government organisations, academic groups, and industry researchers. In March, the World Health Organisation initiated the "SOLIDARITY Trial" to assess the treatment effects of four existing antiviral compounds with the most promise of efficacy.

There has been a great deal of COVID-19 research, involving accelerated research processes and publishing shortcuts to meet the global demand. To minimise the impact of misinformation, medical professionals and the public are advised to expect rapid changes to available information, and to be attentive to retractions and other updates.

វ៉ាក់សាំង

There is no available vaccine, but various agencies are actively developing vaccine candidates. Previous work on SARS-CoV is being used because both SARS-CoV and SARS-CoV-2 use the ACE2 receptor to enter human cells. Three vaccination strategies are being investigated. First, researchers aim to build a whole virus vaccine. The use of such a virus, be it inactive or dead, aims to elicit a prompt immune response of the human body to a new infection with COVID‑19. A second strategy, subunit vaccines, aims to create a vaccine that sensitises the immune system to certain subunits of the virus. In the case of SARS-CoV-2, such research focuses on the S-spike protein that helps the virus intrude the ACE2 enzyme receptor. A third strategy is that of the nucleic acid vaccines (DNA or RNA vaccines, a novel technique for creating a vaccination). Experimental vaccines from any of these strategies would have to be tested for safety and efficacy.

On 16 March 2020, the first clinical trial of a vaccine started with four volunteers in Seattle, United States. The vaccine contains a harmless genetic code copied from the virus that causes the disease.

Antibody-dependent enhancement has been suggested as a potential challenge for vaccine development for SARS-COV-2, but this is controversial.

Medications

At least 29 phase II–IV efficacy trials in COVID‑19 were concluded in March 2020 or scheduled to provide results in April from hospitals in China. There are more than 300 active clinical trials underway as of April 2020. Seven trials were evaluating already approved treatments, including four studies on hydroxychloroquine or chloroquine. Repurposed antiviral drugs make up most of the Chinese research, with nine phase III trials on remdesivir across several countries due to report by the end of April. Other candidates in trials include vasodilators, corticosteroids, immune therapies, lipoic acid, bevacizumab, and recombinant angiotensin-converting enzyme 2.

The COVID‑19 Clinical Research Coalition has goals to 1) facilitate rapid reviews of clinical trial proposals by ethics committees and national regulatory agencies, 2) fast-track approvals for the candidate therapeutic compounds, 3) ensure standardised and rapid analysis of emerging efficacy and safety data and 4) facilitate sharing of clinical trial outcomes before publication.

Several existing medications are being evaluated for the treatment of COVID‑19, including remdesivir, chloroquine, hydroxychloroquine, lopinavir/ritonavir, and lopinavir/ritonavir combined with interferon beta. There is tentative evidence for efficacy by remdesivir, as of March 2020. Clinical improvement was observed in patients treated with compassionate-use remdesivir. Remdesivir inhibits SARS-CoV-2 in vitro. PhaseIII clinical trials are underway in the U.S., China, and Italy.

In 2020, a trial found that lopinavir/ritonavir was ineffective in the treatment of severe illness. Nitazoxanide has been recommended for further in vivo study after demonstrating low concentration inhibition of SARS-CoV-2.

There are mixed results as of 3 April 2020 as to the effectiveness of hydroxychloroquine as a treatment for COVID‑19, with some studies showing little or no improvement. The studies of chloroquine and hydroxychloroquine with or without azithromycin have major limitations that have prevented the medical community from embracing these therapies without further study.

Oseltamivir does not inhibit SARS-CoV-2 in vitro and has no known role in COVID‑19 treatment.

Anti-cytokine storm

Cytokine release syndrome (CRS) can be a complication in the later stages of severe COVID‑19. There is preliminary evidence that hydroxychloroquine may have anti-cytokine storm properties.

Tocilizumab has been included in treatment guidelines by China's National Health Commission after a small study was completed. It is undergoing a phase2 non-randomised trial at the national level in Italy after showing positive results in people with severe disease. Combined with a serum ferritin blood test to identify cytokine storms, it is meant to counter such developments, which are thought to be the cause of death in some affected people. The interleukin-6 receptor antagonist was approved by the FDA to undergo a phase III clinical trial assessing the medication's impact on COVID‑19 based on retrospective case studies for the treatment of steroid-refractory cytokine release syndrome induced by a different cause, CAR T cell therapy, in 2017. To date, there is no randomised, controlled evidence that tocilizumab is an efficacious treatment for CRS. Prophylactic tocilizumab has been shown to increase serum IL-6 levels by saturating the IL-6R, driving IL-6 across the blood-brain barrier, and exacerbating neurotoxicity while having no impact on the incidence of CRS.

Lenzilumab, an anti-GM-CSF monoclonal antibody, is protective in murine models for CAR T cell-induced CRS and neurotoxicity and is a viable therapeutic option due to the observed increase of pathogenic GM-CSF secreting T-cells in hospitalised patients with COVID‑19.

The Feinstein Institute of Northwell Health announced in March a study on "a human antibody that may prevent the activity" of IL-6.

Passive antibodies

Transferring purified and concentrated antibodies produced by the immune systems of those who have recovered from COVID‑19 to people who need them is being investigated as a non-vaccine method of passive immunisation. This strategy was tried for SARS with inconclusive results. Viral neutralisation is the anticipated mechanism of action by which passive antibody therapy can mediate defence against SARS-CoV-2. Other mechanisms, however, such as antibody-dependent cellular cytotoxicity and/or phagocytosis, may be possible. Other forms of passive antibody therapy, for example, using manufactured monoclonal antibodies, are in development. Production of convalescent serum, which consists of the liquid portion of the blood from recovered patients and contains antibodies specific to this virus, could be increased for quicker deployment.