ABSTRACT
Today, nanotechnology has been studied in various fields of science. The field of vaccines is one of the areas that is being more attention today due to the COVID-19 pandemic (1). Nanoparticles can play both an adjuvant and a delivery roles in vaccine systems and also nanotechnology-based vaccines can stimulate both the humoral and cell-mediated immune responses (2). There are several companies involved in the production of Covid 19 vaccine, two of which, Pfizer-BioNTech and Moderna, have been able to produce vaccines based on nanotechnology and mRNA. The above-mentioned companies have used lipid nanoparticles as a vaccine delivery system in their formulations. The lipid nanoparticles promote endosomal escape, prevention of enzymatic degradation and release their genetic cargo in the cytosol, where the mRNA is translated into proteins that can play an antigenic role and stimulate the immune system. The success of Pfizer-BioNTech (BNT162b2) and Moderna (mRNA-1273) vaccines with ~95% efficacy in phase III clinical trials can be attributed to their especial nanocarrier, the "lipid nanoparticles"(3-5). © 2021, Shahroud University of Medical Sciences. All rights reserved.
ABSTRACT
Objectives: COVID-19 is a worldwide health problem. Although the most infected patients experience a mild-to-moderate disease, some patients (especially older people) develop pulmonary distress with fatal lung failure and multi-organ damage. There is currently no known effective treatment for this disease. Sofosbuvir, an FDA-approved drug for the treatment of hepatitis C virus, is also able to inhibit other members of positive strand RNA viruses with conserved polymerase and may be helpful for the treatment of SARS-CoV-2. The goal of the current trial is to determine the usefulness of 'standard of care (SOC) plus hydroxychloroquine and lopinavir/ritonavir' vs. 'SOC plus a combination of lopinavir/ritonavir hydroxychloroquine and sofosbuvir/velpatasvir' in patients hospitalized with COVID-19. The Design of Clinical Trial: In this randomized controlled trial, patients over 18 years who have been diagnosed with COVID-19 by the positive SARS-CoV-2 reverse transcriptase-polymerase chain reaction (RT-PCR) test or compatible chest computed tomography (CT) scan were candidates for the study. Eighty patients from Kermanshah province, West of Iran were allocated to treatment with SOC plus hydroxychloroquine and lopinavir/ritonavir (dual therapy) or SOC plus a combination of hydroxychloroquine and lopinavir/ritonavir and sofosbuvir/velpatasvir (triple therapy) for 10 days. Allocation was conducted using simple randomization. The primary outcomes were reducing mortality up to 28 days after hospitalization. Adverse events were handled and reported in accordance with the Good Clinical Practice guidelines. Participants: Patients who were hospitalized with COVID-19 (with positive SARS-CoV-2 RT-PCR test and/or compatible chest CT scan) were screened for eligibility at Farabi Hospital, Kermanshah University of Medical Sciences (KUMS), Kermanshah, Iran. Intervention and Comparator: Both arms received active treatment and none was given placebo. The intervention arm received hydroxychloroquine 400 mg single dose and lopinavir-ritonavir (400 and 100 mg) twice daily plus sofosbuvir-velpatasvir (400 and 100 mg) once daily orally, plus SOC for 10 days. The comparator arm received hydroxychloroquine 400 mg single dose and lopinavir-ritonavir (400 and 100 mg) twice daily orally, plus SOC for 10 days. SOC includes oxygen therapy, non-invasive and invasive ventilation, antibiotic agents, vasopressor support, renal-replacement therapy, and corticosteroids. Primary Outcomes: The main outcomes are reducing mortality until 28 days after hospitalization. Other outcomes can be found in full protocol file. Randomization: For the purpose of allocation sequence generation, using an Excel file (random-numbers table) and simple random allocation, 80 included patients entered to the study, 40 patients in each group (1:1 ratio). In order to maintain the allocation sequence concealment, the details of treatment for each patient were contained in a sealed envelope, labeled by the numbers from 1 to 80. In fact, our study was a randomized open label clinical trial in which all the physicians and nurses plus all patients were aware of the type of treatment. Blinding: Our study was a randomized open label clinical trial in which all the physicians and nurses plus all patients were aware of the type of treatment. Numbers to be Randomized (Sample Size): Eighty included patients entered to the study, 40 patients in each group using simple random allocation. Trial Status: The finalized protocol version 1.5 was used in the trial study and the recruitment/intervention process started on April 11, 2020, finished on May 11, and the related follow-up finished on June 8, 2020. Registry of Clinical Trial: This clinical trial has been registered on March 30, 2020 under IRCT number 46790, in the Iranian Registry of Clinical Trials (https://www.irct.ir/trial/46790) and by KUMS under Grant No. 990097. Full Protocol: The full protocol and other details are attached as a Supplementary File (full protocol), accessible from the journal website. Preliminary Data: The sofosbuvir/ve patasvir regimen does not improve survival, clinical improvement, and duration of hospitalization in hospitalized COVID-19 patients.
ABSTRACT
COVID-19 is a virus that causes acute respiratory syndrome. Although it is less deadly than other members of its family, i.e. SARS and MERS, its extremely rapid transmission rate has become a widespread concern today. Airborne droplets, environmental surfaces, nasal mucosa, urine and fecal samples are among the routes for the transmission of this virus. Both temperature and humidity factors affect the viability of the virus and its mortality rate. Increasing the ambient temperature makes the virus unstable, while lowering the temperature contributes to its stability. Due to the fact that the main route for the transmission of this virus is the particles containing the virus, observing the social distance of at least one meter, using masks as well as air purification systems can reduce the risk of virus transmission to some extent. This contagious virus has made life difficult for everyone in the community, especially pregnant women, children and the elderly. This viral infection can be diagnosed in many ways, including laboratory tests, molecular tests, the chest X-ray and CT scan. It is worth noting that chest CT scan is more sensitive than other methods and is used as the first line of diagnosis. Despite numerous efforts, no definitive cure has yet been found and isolation of those involved is recognized as first-line treatment. The treatments so far can be divided into three categories: general treatments, pharmacological treatments, and diet. General treatments involve isolation, mask use, oxygen therapy, room ventilation and more. Because of the rapid spread and the many challenges that this viral infection has created, scientists have used many of the drugs that were previously used to treat the influenza, malaria, AIDS, etc., some of which have been used to treat the viral infection. It should be noted that some of these drugs were very effective on some people's bodies. Some of these drugs were even used for pregnant mothers. A proper diet and the use of certain vitamins such as iron, zinc, vitamins A, B, C, E can also be effective in preventing and treating this viral infection. Many efforts to develop a vaccine against this virus infection began about two weeks after the outbreak and the attempts to reach this goal continues. © 2020, Dorma Journals. All rights reserved.